All USH News
Here you will find an archive of all news and announcements impacting the Usher community.
Dr. Corey's goal is to rescue vision, but he is testing first on hearing because it’s easier to measure in a mouse model. Because babies with Usher 1 are born profoundly deaf but sighted, researchers believe that the hearing is more sensitive to the absence of the protein than vision. Therefore, if a gene therapy rescues hearing, theoretically, it should also rescue vision.
Martha Neuringer, Ph.D., leads the research team at OHSU, Oregon Health & Science University, that confirmed the first-ever nonhuman primate model of Usher syndrome.
Dr. Neuringer's lab created a monkey with the MYO7A mutation that causes Usher Type 1B. For the first time, an animal model demonstrates all three phenotypes of USH1B: deafness, impaired balance and retinal degeneration.
This is significant because primates are the closest genetic cousins to humans, and having this animal model allows scientists to better understand Usher syndrome and test potential treatments.
In 2022, the Usher Syndrome Coalition partnered with ProQR to provide outreach and education for their clinical trial. That trial is now paused. Here are some steps you can take to make sure you're ready for future clinical trials.
With IP Relay, DeafBlind users can make and receive calls and communicate the way they want to whenever they need to. But what is IP Relay?
Researchers at the National Eye Institute (NEI) have found that the cells that make up the retinal pigment epithelium (RPE, cells in the retina that supports the photoreceptors) have 5 distinct subpopulations.
Researchers at the John A. Moran Eye Center at the University of Utah and Scripps Research have used the retina to study how neurons die and how they can be revived.
Parenting, in general, is filled with challenges. Being a parent with Usher syndrome can add another layer of complexity. Here, USH moms share their advice for parenting with Usher.
West Virginia University (WVU) received an $11 million grant from the National Institutes of Health (NIH) to establish a new visual sciences Center of Biomedical Research Excellence (COBRE).
Currently, there is an unmet need for technologies to treat vision loss because of photoreceptor degeneration. Researchers at the University of Southern California (USC) have come up with a new idea.
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Researchers led by Richard Kramer at the University of California, Berkeley, have discovered that Antabuse (disulfiram), which was a drug that use to be used to wean alcoholics off of drinking is also able to help improve sight in mice with retinal degeneration.
Tom, a member of our Usher community shares some tips that he has found helpful as an older adult with Usher syndrome type 2a. Please note that these tips may not be applicable for everyone as this is written from the experience of one person.
India times wrote an opinion piece about the futuristic aspect of bionic eyes research progression.
Researchers at the University of Wisconsin School of Medicine and Public Health were able to create retinal cells from human stem cells that can detect light and change it to electrical waves.
Bionic Vision Technologies, a company in Australia has created the world’s first bionic eye that can restore partial, functional vision to people who have lost their vision due to retinitis pigmentosa (RP).
Announcing our partnership with ProQR to support clinical trial enrollment for a potential therapy for USH2A mediated retinitis pigmentosa
Researchers in China successfully created an induced-pluripotent stem (iPS) cell line using immune cells from the blood of a patient with Usher syndrome type 2A.
The FDA and National Institutes of Health (NIH) are partnering with 15 private organizations to increase the number of gene therapies for rare diseases.
The Atlantic Journal-Constitution summarizes research being done in Switzerland at Paul Scherer Institute on a protein, cyclic nucleotide-gated ion channel, in the eye.
Researchers at Newcastle University are looking into creating treatments for common inherited eye conditions.
The biopharmaceutical company, Ocugen Inc., has announced that the FDA has accepted their Investigational New Drug (IND) application to start a human clinical trial with OCU400.
A recent biotechnology breakthrough is the organ-on-chip (OOC) technology.
AIVITA Biomedical Inc., a biotech company that specializes in new ways of using stem cells, recently conducted a preclinical study. Using human stem cells that they created, researchers created and tested a “total retina patch” for vision loss.
Professor Gregg Suaning has been working for more than 20 years to help restore vision. Currently, he is working on a technology similar to cochlear implants; a pair of glasses that has a camera attached to them.
The National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), 10 pharmaceutical companies, and five non-profits have partnered as the Bespoke Gene Therapy Consortium (BGTC) to help speed up the development of gene therapies for rare diseases.
Scientists have developed a type of “pellet” implant that can be injected into the eye to prevent cataracts from forming.
University of Pittsburgh School of Medicine is working on a technology to help other researchers determine what the best gene delivery system could be for their genetic treatment research.
Eye drops of PNU-282987, an α7 nicotinic acetylcholine receptor agonist, were shown to support regeneration of retinal neurons in mice.
Often, individuals who present with deafness and vision loss are assumed to have Usher syndrome (USH). This assumption is not correct.
Becca Meyers is the only Paralympic swimmer on Team USA who is both deaf and blind. This dual sensory loss has far-reaching effects on an individual’s quality of life and engagement in society. We invite the USOPC to join together with the Usher Syndrome Coalition and other organizations supporting the deafblind community to address and resolve the underlying issues resulting in the denial of Ms. Meyers’s request for essential accommodation.
Researchers have been exploring stem cell therapies to treat vision loss, including vision loss caused by retinitis pigmentosa. Preclinical and clinical studies are showing that stem cell therapies could be new options.
A Phase 2 clinical trial was used to see if injecting human retinal progenitor cells (derived from stem cells) can improve vision and visual fields in people with retinitis pigmentosa (RP).
Nanoscope Therapeutics Inc. announced that in their Phase 1/2a clinical study, a year following a single injection of Multi-Characteristic Opsin (MCO) into the eye, there was vision improvement in all patients with retinitis pigmentosa (RP). The MCO gene used in the study is delivered into the retina using AAV2 vectors. 3 patients received low dosage injections and 8 received high dosage. All patients in this study had objective and subjective improvements in functional vision. There was also improvement seen in mobility tests. Most opsins have a limited scope of clinical benefit because they have a narrow band of activation. MCO is sensitive to broadband light and can react to ambient lighting so there is no need for an external light device.
What this means for Usher syndrome: This new therapy seems to be able to restore some vision in patients with RP regardless of the type of mutation that causes it. Because vision loss in Usher syndrome is a type of RP, this new therapy could be beneficial to Usher syndrome patients.
Usher syndrome (USH) is the most common form of genetic deaf-blindness. Thus far there are no treatments for vision loss. Researchers were able to create a pig model for USH1C by introducing a human mutation into the USH1C gene in pigs. This successfully created an animal model with the hearing defect, vestibular dysfunction, and visual impairment found in USH. The primary cell isolated from these pig models and USH1C patients show elongated primary cilia compared to primary cells with no USH mutations. This finding confirms USH as a genetic disorder that affects cilia. The research also proves that there can be therapeutic benefits in gene supplementation and gene repair therapies.
What this means for Usher syndrome: Researchers have now confirmed that USH is a genetic disorder affecting cilia. Knowing this enables possible therapies like gene supplementation and gene repair.
The company, Vedere Bio II, is working on optogenetic gene therapies based largely on the work of University of California, Berkeley, neuroscientists Ehud Isacoff and John G. Flannery to restore vision.
Individuals that have permanent damage to their photoreceptors are unable to repair or regenerate new photoreceptors. Researchers and engineers may have a possible solution for these individuals living with vision loss. They have worked to make new photoreceptors and a micro-molded scaffolding photoreceptor “patch.”
Magdalene Seiler, Ph.D., UCI associate professor has been awarded a five-year grant of $3,823,950 from the National Institutes of Health to do a preclinical study using rodent models. This study looks at an innovative co-graft method to permanently repair damaged retinas.
ProQR has published positive results from its Phase 1/2 Stellar trial of QR-421a, an investigational RNA therapy for the treatment of Usher syndrome and retinitis pigmentosa (RP) due to mutation(s) in exon 13 of the USH2A gene.
FDA grants special status to a new cell therapy that chemically converts cells into photoreceptor-like cells with partial restoration of pupil reflex and visual function.
Researchers at Ecole Polytechnique Federale de Lausanne have developed a retinal implant with electrodes for individuals who become blind due to photoreceptor cell loss. The implant is paired with smart glasses that together provides artificial vision.
Second Sight Medical Products has recently announced that the FDA has approved of their Argus 2s Retinal Prosthesis System. This is a visual aid intended to assist individuals with retinitis pigmentosa (RP).
Photoreceptor precursor cells that were generated from stem cells were able to be successfully transplanted into the retina and demonstrate basic visual function.
Retinitis pigmentosa (RP) affects the photoreceptors in the back of the eye. Specifically, the rods are damaged first, which results in the typical symptom presentation of difficulty seeing in dim lighting and progressive tunnel vision. In this study, researchers at Harvard University explore the relationship between RP & cone damage in the hopes that a non-genetic-based treatment can be developed to protect against the later end-stage disease symptoms.
In a recent study, retinal cells coming from adult human eye stem cells were successfully put into the eyes of monkeys.
An interdisciplinary team of scientists funded by University of Toronto’s Medicine by Design initiative believes they can improve the outcomes of conditions like age-related macular degeneration and retinitis pigmentosa.
HyVIS (Hybrid synapse for VISion) is an EU-funded initiative launched with the goal of developing a method to restore sight in people with degenerative eye diseases like retinitis pigmentosa.
A team of researchers at Tel Aviv University are studying a virus-based gene therapy approach to treat deafness by replacing the non-functioning gene with a functional copy.
Journalists at Fierce Biotech summarized exciting research from the Centre for Genomic Regulation in Barcelona. They are studying how stem cell biotechnology can be improved in retina disease treatment models.
Usherin, a protein associated with the USH2A gene that causes Usher Syndrome Type 2A, helps us see and hear. A new study has discovered that this protein may also be involved in a third sense – the sense of touch. Researchers found Usherin protein in the “Meissner corpuscle”, which is a nerve ending in the skin of our fingers. When the production of Usherin is affected due to a mutation in the USH2A gene, this results in Usher syndrome, with known impairments in vision and hearing. It is now thought also to be involved with touch. Experiments were performed with two groups of mice, with and without the USH2A gene. Both groups of mice were able to detect temperature changes and pain, but the mice with USH2A were better at detecting low levels of vibrations than the mice without this gene.
What this means for Usher syndrome:
This discovery increases our understanding of the USH2A gene, the Usherin protein, and how they are connected to our senses. These insights may lead to additional research and discoveries that may one day, turn into a cure for Usher syndrome.
Researchers in China have identified a new USH2A gene mutation in an individual with Usher syndrome type 2. Mutations are genetic changes that affect the proper function of the gene and/or the protein it encodes. Identifying and understanding a genetic mutation is important because it opens up the possibility of gene therapy in the future. Here, the researchers used a technique called targeted exome sequencing (TES), where they analyzed thousands of genes at one time to look for changes or new information. In this case, they found that this new mutation blocks important proteins from being made. This new discovery not only provides more insights into the causes of Usher Syndrome Type 2A, but also demonstrates advantages that TES can bring to Usher syndrome researchers.
What this means for Usher syndrome:
With the discovery of this new mutation, researchers are continuing to learn more about Usher syndrome and the causes behind it. Over time, this may lead to new gene therapies, treatments, or possibly a cure one day.
Case study and one year follow up on five patients with end-stage RP that received retinal implants.
Lentivirally modified mesenchymal stem cells from bone marrow shows promise in preserving retinal function and preventing further retinal degradation.
Researchers have found that using liposomes triggered by light to deliver CRISPR gene therapy, rather than viruses, is a safer and more targeted method.
Vedere Bio, Inc., a company focused on photoreceptor-protein-based optogenetic therapies (use of light to modulate neurons that have been genetically modified) to restore vision has been acquired by Novartis.
The National Eye Institute, part of the National Institutes of Health, had provided a research grant to Nanoscope, LLC for their development of MCO1.
In a proof-of-concept study, researchers found evidence of the potential of base editors to correct mutations that cause inherited retinal diseases (IRD).
Two scientists, Emmanuelle Charpentier and Jennifer Doudna, have been awarded the 2020 Nobel Prize in Chemistry for developing the tools to edit DNA. They are the first two women to share the prize, which honors their work on the technology of genome editing. During Professor Charpentier’s studies of bacterium Streptococcus pyogenes, she discovered a previously unknown molecule called tracrRNA, which is part of the organism’s immune system. This system, now known as CRISPR/Cas9, disrupts viruses by cleaving (or cutting) their DNA – like genetic scissors. Drs. Charpentier and Doudna together recreated this system in a test tube and showed it can be reprogrammed to cut any DNA molecule at a predetermined site. Since this discovery, the CRISPR/Cas9 gene editing system has already contributed to many important discoveries in basic research; and is currently being investigated for its potential to treat sickle cell anaemia, a blood disorder that affects millions of people worldwide. In medicine, clinical trials of new cancer therapies are underway, and this technology may also have the potential to treat or even cure inherited diseases.
What this means for Usher syndrome: Researchers have already started to evaluate the use of CRISPR/Cas9 gene editing to target specific mutations in patients with USH2A. Successful in-vitro (outside the body) mutation repair was demonstrated with proven effectiveness and specificity. This indicates the CRISPR/Cas9 gene editing system shows promise and should be further explored as a potential treatment for Usher syndrome.
Delivery of therapeutic genes into retina is proving to reverse degeneration and restore vision, however, viral vector-based gene delivery is prone to immunorejection, inflammatory/immune-response and nontargeted. Here, we report nonviral gene delivery and expression of opsin encoding genes in mouse retina in-vitro and in-vivo by use of pulsed femtosecond laser microbeam. In-vitro patch-clamp recording of the opsin-sensitized retinal cells and visually evoked in-vivo electrical recording from laser-transfected eye of mouse with degenerated retina showed functional response. The ultrafast laser-based naked gene delivery showed minimal damage and reliable expression of therapeutic opsin in cell membrane of the selected cells and in targeted retinal region. Laser-based "naked DNA gene therapy" in a spatially targeted manner will pave the way for treatment of inherited retinal diseases.
What this means for Usher syndrome: Based on this study, laser-based delivery of gene therapy appears to be a viable alternative to viral-vector based gene delivery with less adverse effects. In the future, this may translate into more, and safer, treatment options for Usher patients.
Eyevensys, a biotechnology company developing non-viral gene therapies for ophthalmic diseases, today announced the U.S. Food and Drug Administration (FDA) has granted an orphan-drug designation (ODD) for EYS611 for the treatment of retinitis pigmentosa (RP). EYS611 is a DNA plasmid that encodes for the human transferrin protein which helps manage iron levels in the eye. While iron is essential for retinal metabolism and the visual cycle, too much iron is extremely toxic to the retina and has been associated with photoreceptor death in several retinal degenerative diseases. By acting as an iron chelating and neuroprotective agent (an agent that reduces level of toxic metals in the blood and tissues), EYS611 helps slow the progression of diseases like RP regardless of the specific genetic mutation causing the condition. This can potentially benefit patients diagnosed with RP, as well as other degenerative retinal diseases, including late stage, dry age-related macular degeneration and glaucoma. Eyevensys just reported data from preclinical testing in the September 2020 issue of the journal Pharmaceutics. The paper, entitled “Transferrin non-viral gene therapy for treatment of retinal degeneration” (Bigot, et al., Pharmaceutics), shows that EYS611 is safe and effective for preserving photoreceptors and retina functionality in acute toxicity and inherited rat models of retinal degeneration.
What this means for Usher syndrome: The orphan-drug designation by the FDA means that Eyevensys has been granted a seven year window to exclusively develop EYS611. This gene therapy is intended for all RP patients regardless of the underlying mutation, is less invasive than viral-vector gene therapies, and can be used at earlier stages of the disease. Since this is not mutation specific, this non-viral gene therapy will be a viable option for Usher patients.
Intravitreal injection of human retinal progenitor cells (hRPCs;jCells) is a novel stem cell treatment currently in development for retinitis pigmentosa (RP. In a recently completed phase 2b study, this treatment was injected into the jelly-like center or vitreous of the eye and has demonstrated promising biologic activity and an excellent safety profile. In this study, 84 patients diagnosed with RP and with best-corrected visual acuity (BCVA) between 20/80 to 20/800 were randomly assigned to 2 different doses (low or high) of jCells or a placebo. The primary end point (or target outcome) was the mean change in the BCVA at 12 months; the secondary end points were identification of the lowest light level at which patients could navigate through a structured mobility maze, along with the mapping of each patient’s kinetic visual field, the evaluation of their performance on contrast sensitivity testing, and completion of a low vision–specific quality-of-life questionnaire. In a post hoc analysis of this target population, an early and significant improvement in vision was seen in the higher-dose group, with average gain of 16 letters at month 12 compared with 2 letters in the control group. Improvement in the higher-dose group compared to the control group was also true for the secondary outcomes. While there were some mild cases of eye inflammation and one severe case of hypertension associated with treatment, these adverse effects were addressed. These study results showed that intravitreal injection of allogeneic jCells that were not derived directly from the patient shows promising results. The study is expected to continue with expected redosing of patients and further monitoring as this treatment is not expected to be permanent.
What this means for Usher syndrome: These results from a Phase 2b study demonstrate that intravitreal injection of retinal progenitor stem cells shows measurable improvement in vision and may be a viable treatment option in the future for both Usher and RP patients.
Results for the Phase I study for the NR600 Implant seems to show that this retinal prosthesis is safe for patients that have end-stage retinitis pigmentosa (RP).
LambdaVision, a biotech company that is developing a treatment to help patients regain sight, will launch their artificial retina technology with engineering partner Space Tango on Northrop Grumman’s 14th Commercial Resupply Services Mission for NASA (NG-14) to the International Space Station (ISS) U.S. National Laboratory. Scheduled to launch on September 30th at 10:26 p.m. ET, NG-14 is the first of a series of NASA flights to the ISS in low-Earth orbit (LEO) focused on developing the on-orbit production of LambdaVision’s artificial retina. LambdaVision’s research on the ISS focuses on exploring the benefits of microgravity for producing its artificial retina, and expands on research being conducted on Earth and previous efforts on the ISS. Initial studies will evaluate the effects of microgravity on protein function and stability, which is critical for the quality and performance of the artificial retina. Outcomes of this experiment will provide a foundation for future ISS-based trials. Over the next three years, the LambdaVision-Space Tango partnership will serve to evaluate and improve on-orbit production processes, and to produce artificial retinas that will then be evaluated on Earth.
What this means for Usher syndrome: Artificial retinas are intended for individuals who have lost their vision due to degenerated photoreceptor cells, but still possess functional or intact retinal nerve cells and optic nerves. If LambdaVision's unique approach to on-orbit production successfully delivers high quality and high performing artificial retinas, Usher patients may one day be able to regain some of their sight.
Scientists from Australia's Monash University, who spent more than a decade developing a bionic vision system where signals from a wireless brain implant are transmitted to a camera mounted on a special pair of glasses, are gearing up for human clinical trials. The Gennaris bionic vision system is a unique solution that completely bypasses the eye, and do not require wires to protrude through the scalp. A small microchip is implanted on the surface of the brain and can generate 172 different bright spots called phospenes, in order to provide visual cues to the user about what is in front of them. This innovative technology within the Gennaris system has been previously tested on sheep, yielding very positive results and no noticeable side effects after more than 2700 hours of visual stimulation. While the Gennaris system is designed specifically to restore vision, the technology has potential for other applications, such as overcoming paralysis by bypassing injured nerves and connecting affected limbs directly to the brain.
What this means for Usher Syndrome: The Gennaris system is intended to restore limited vision to the blind, regardless of the cause. Therefore, if proven successful, this bionic vision system will be an option for Usher patients in addition to those with retinitis pigmentosa and other visual impairments.
This year’s Körber Prize for European Science was given to a Hungarian scientist whose revolutionary gene-editing treatment could cure a type of blindness that affects around one in 4,000 children. Cell biologist Botond Roska’s pioneering work on the human retina has placed him among the world leaders in the study of ophthalmology—work that included the presumably painstaking effort of identifying over 100 different retina cell types and their complex interrelations. His work on novel gene therapies has led to discovery of a possible cure for retinitis pigmentosa. Roska’s work which involves the reprogramming of retina cells into photoreceptors, thereby taking over from the damaged ones and restoring light and color in blind retina, is currently going through clinical trials. As a result of this ground-breaking discovery, he was granted the prestigious award of €1 million.
What this means for Usher syndrome: If proven successful, this novel gene therapy may restore partial vision to affected Usher patients by enabling previously blind retinas to detect light and color.
This 2020 review summarizes how research efforts have advanced greatly allowing medical professionals to make diagnoses quicker.
Our overall health including mental health is important to monitor and be aware of regardless of what health condition we may have. This article covers how having Usher Syndrome may affect someone's mental health, social life as well as their financial health.
Researchers discovered an ingredient (TMP) found in a Chinese herb (chuanxiong) could have anti-inflammatory properties.
Researchers have discovered a technique for directly reprogramming skin cells into light-sensing rod photoreceptors used for vision. The laboratory-made rods enabled blind mice to detect light after the cells were transplanted into the animals’ eyes. According to Anand Swaroop Ph.D., senior investigator, “This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors.” The immediate benefit of this technique will be the ability to develop models to allow us to study the mechanisms of the disease and design better cell replacement approaches. Induced pluripotent stem (IPS) cells take about six months to create, however direct reprogramming takes only about ten days to convert skin cells into functional photoreceptors. A clinical trial to test the therapy in humans for degenerative rental diseases such as retinitis pigmentosa is in the works.
What this means for Usher syndrome: This new technique holds promise for treatment of many retinal degenerative diseases, including Usher syndrome.
Stem cell technology has enabled new possibilities for understanding and treating rare diseases such as Usher syndrome. The technology for stem cell treatment is still relatively new and complex. Unfortunately, several private clinics are attempting to financially capitalize on patients’ desperation and confusion for a cure. David Gamm, MD, PhD, a researcher at the University of Wisconsin-Madison, wrote an article for Foundation Fighting Blindness explaining the ten things we should know before falling victim to a retinal stem cell scam. Even if the treatment does not cause physical harm, it can result in significant financial damage; therefore, it is important to be aware of these scams.
ProQR Therapeutics announces positive findings from a planned three-month interim analysis of its Phase I/II Stellar trial of QR-421a to treat retinitis pigmentosa (RP) in adults who have Usher syndrome type 2 or non-syndromic RP due to mutations in a specific part of the USH2A gene, called exon 13. QR-421a, ProQR’s experimental RNA therapy is designed to skip exon 13 in the RNA with the aim to stop or reverse vision loss. QR-421a given as a single intravitreal injection was safe and well-tolerated. It also showed early and encouraging evidence of activity, with 25% of patients showing a benefit across multiple outcome measures.
What this means for Usher syndrome: While this particular experimental drug is only applicable to those with Usher syndrome due to mutation(s) in exon 13 of the USH2A gene, early positive findings mean that the trial will continue as designed and could lead to other RNA/drug therapies that will benefit people with Usher syndrome caused by other mutations.
For the first time, scientists have used the gene-editing technique CRISPR to try to edit a gene while the DNA is still inside a person’s body. The procedure involved injecting the microscopic gene-editing tool into the eye of a patient blinded by a rare genetic disorder, in hopes of enable the participant to see. Researchers hope to know within weeks with the approach is working and, if so, to know within two or three months how much vision will be restored.
What this means for Usher syndrome: If successful, this will be a huge step forward towards the development of therapies to restore vision in Usher patients.
Ocugen Inc., a clinical-stage company focused on discovering, developing, and commercializing transformative therapies to treat rare ophthalmic diseases, announced today in the publication in 'Nature Gene Therapy' preclinical data of nuclear hormone receptor gene NR2E3 as a genetic modifier and therapeutic agent to treat multiple retinal degenerative diseases. The publication details efficacy results in five different mouse models of RP that underwent administration of NR2E3-AAV by subretinal injection. The study demonstrates the potency of a novel modifier gene therapy to elicit broad-spectrum therapeutic benefits in early and intermediate stages of RP.
What this means for Usher syndrome: This gene modifier has been successfully tested in five genetic mouse models for RP. Although nothing is known regarding the involvement of this modifier in Usher syndrome, it will be interesting to know whether this modifier can rescue photoreceptor activity in animal models for Usher syndrome. If it does, it will mean it can be used in gene therapy or as a drug target.
Allergan, a global pharmaceutical company, and Editas Medicine, a genome editing company, have announced treatment of the first patient in the BRILLIANCE clinical trial for AGN-151587 (EDIT-101) at Oregon Health & Science University (OHSU) Casey Eye Institute. AGN-151587 is a CRISPR-based experimental medicine under development for the treatment of Leber congenital amaurosis 10 (LCA10), an inherited form of blindness cau sed by mutations in the centrosomal protein 290. This potential treatment targets photoreceptor cells and is delivered via sub-retinal injection. The BRILLIANCE clinical trial is the world’s first human study of an in vivo (inside the body) CRISPR genome editing medicine, and is currently in Phase I/2 to assess the safety, tolerability, and efficacy of AGN-151587 in approximately 18 patients with LCA10.
What this means for Usher syndrome: If the clinical trial is successful, this CRISPR-based treatment which targets photoreceptor cells may be an option for other forms of blindness, including Usher syndrome.
In this study, a nuclear hormone receptor (NHR, a type of protein) gene Nr2e3 was tested as a possible general therapy to reduce the effects of early to intermediate stages of retinal degeneration in five mouse models of retinitis pigmentosa (RP).
The ReNeuron Group has announced positive long-term data from its ongoing phase 1/2a clinical trial of its hRPC (human retinal progenitor cells) stem cell therapy candidate in Retinitis Pigmentosa. In October 2019 at the American Academy of Ophthalmology Meeting in San Francisco, data presented by Pravin Dugel, MD showed “a group of subjects who had a successful surgical procedure with sustained clinically relevant improvements in visual acuity compared with baseline, as measured by the number of letters read on the ETDRS chart.” The company has submitted a protocol amendment to the FDA to expand their 1/2a study to treat up to a further nine patients in the phase 2a segment of the study with a dose of two million hRPC cells compared to the dose of one million cells used so far. The amended trial protocol allows for a greater range of pre-treatment baseline visual acuity in patients and includes changes that enhance the ability to use microperimetry testing to measure and detect changes in retinal sensitivity in patients treated. If the amendment is approved the company expects to have sufficient data to commence a pivotal clinical study with its hRPC cell therapy candidate in RP by 2021. Furthermore, this clinical program has been granted Orphan Drug Designation in Europe and the US, as well as Fast Track designation from the FDA.
What this means for Usher syndrome:That Usher patients may benefit from this stem cell therapy in the near future if the amendment is approved and the company obtain sufficient data for the initiation of the pivotal clinical trial .
Gene-infused nanoparticles used for combating disease work better when they include plant-based relatives of cholesterol because their shape and structure help the genes get where they need to be inside cells. The type of nanoparticle used to deliver genes in this study has already been clinically approved; it's being used in a drug given to patients with a progressive genetic condition called amyloidosis.
What this means for Usher syndrome: This new nanoparticle composition could be a more efficient alternative strategy to deliver the wild type gene into the photoreceptors of Usher patients.
Usher syndrome, a genetic condition that results in hearing and vision loss in childhood, affects about 4 out of every 100,000 Canadians. Fighting Blindness Canada (FCB) has provided new funding that will allow Vincent Tropepe, the professor and departmental chair of cell and systems biology in the Faculty of Arts & Science, to try to identify the causes of retinal degeneration due to Usher. Tropepe’s lab will focus on a particular protein associated with the mutated gene that is also thought to be crucial to the photoreceptors’ larger support system. If researchers can find defects in this protein and the structure it is part of, they may be able to reveal new mechanisms that maintain the stability and functionality of the photoreceptors.
What this means for Usher syndrome: If they can find an association between photoreceptor survival and this protein, this will lead to novel gene therapy strategies and, maybe to the discovery of therapeutic drugs that will help to stabilize the larger photoreceptor structure when that particular protein is dysfunctional.
Mice born blind have shown significant improvement in vision after undergoing new gene therapy developed by a team of Japanese scientists. This new method is an alternative strategy of gene supplementation, which involves supplementing the defective gene, such as the ones that can lead to inherited retinal degeneration with a healthy one. The healthy gene is delivered through an AAV vector, but the virus can only hold a small healthy gene. Therefore, patients with large genes cannot be treated with this method. This new gene therapy combines AAV vector delivery with CRISPR-Cas9 technology, this way researchers can target a specific defective gene, cut it out and glue in a healthy replacement. This approach rescued 10% of the photoreceptors, resulting in a visual improvement very similar to gene supplementation therapy.
What this means for Usher syndrome: This is an alternative strategy that can be developed into new therapies to treat Usher patients, but only those harboring mutations in the small genes (USH1C, USH1G, DFNB31 and USH3A).
USH2A variants are the most common cause of Usher syndrome type 2, characterised by congenital sensorineural hearing loss and retinitis pigmentosa (RP), and also contribute to autosomal recessive non-syndromic RP. Several treatment strategies are under development, however sensitive clinical trial endpoint metrics to determine therapeutic efficacy have not been identified. In the present study, scientists performed longitudinal retrospective examination of the retinal and auditory symptoms in (i) 56 biallelic molecularly-confirmed USH2A patients and (ii) ush2a mutant zebrafish to identify metrics for the evaluation of future clinical trials and rapid preclinical screening studies. The patient cohort showed a statistically significant correlation between age and both rate of constriction for the ellipsoid zone length and hyperautofluorescent outer retinal ring area. Visual acuity and pure tone audiograms are not suitable outcome measures. Retinal examination of the novel ush2au507 zebrafish mutant revealed a slowly progressive degeneration of predominantly rods, accompanied by rhodopsin and blue cone opsin mislocalisation from 6-12 months of age with lysosome-like structures observed in the photoreceptors. This was further evaluated in the ush2armc zebrafish model, which revealed similar changes in photopigment mislocalisation with elevated autophagy levels at 6 days post fertilisation indicating a more severe genotype-phenotype correlation, and providing evidence of new insights into the pathophysiology underlying USH2A-retinal disease.
What this means for Usher syndrome: If the involvement of autophagy, the body's way of cleaning out damaged cells, is confirmed in RP patients, this means that novel therapies targeting autophagy will help to alleviate the progression of the retinitis pigmentosa in Usher patients.
A team of researchers from Massachusetts Eye and Ear have identified a cellular entry factor for the adeno-associated virus vector (AAV) types—the most commonly used virus vector for in vivo gene therapy. The researchers identified that GPR108, a G protein-coupled receptor, served as a molecular lock to the cell. GPR108 is required for most AAVs, including those used in approved gene therapies, to gain access to the cell. Since gaining cellular access is a crucial step in delivering gene therapy, this discovery may provide a crucial piece of information that could one day enable scientists to better explain, predict, and direct AAV gene transfers to specific tissues.
What this means for Usher syndrome: This discovery may improve the chances for targeting gene therapy for Usher syndrome.
Scientists at the Italian Institute of Technology have created the first-ever artificial retina to be made only from organic materials: a substrate derived from a soy protein, a conductive polymer, and a semiconductor. The retina is designed to work like a solar panel, “converting light into electrical signal, which is transmitted to the retina’s neurons.” Because these artificial retinas are made from organic materials, they should be more compatible and reduce the risk of being rejected by the body after the operation.
What this means for Usher syndrome: This work may one day lead to retinal implants to treat vision loss in Usher patients.
Patients from the same family and carriers of the same genetic mutation, develop a disease differently. This disparity may be due to the existence of mutations in other secondary genes that influences the onset and progression of the disease caused by the primary mutation. Two researchers from Dr. Cerón’s group, Dmytro Kukhtar and Karina Rubio-Peña, from Bellvitge Biomedical Research Institute (IDIBELL), have worked on this topic in the last few years. Utilizing CRISPR gene-editing technology, they introduced in C. elegans worms, mutations that cause RP in humans. Next, these mutations were classified into two groups: those that caused an obvious problem to worms and those that did not. Worms that were not affected by human mutations were used to search for other genes whose inactivation caused alterations in the mutant worms, but not in the control worms. Three genes were identified as candidate disease modifiers that may interact with the primary mutation to affect disease progression. The researchers then identified drugs that were harmful to worms harboring patient mutations, but not control worms.
What this means for Usher syndrome: Although it is important to find drugs that cure, it is also important to identify those drugs that could be harmful to patients with known genetic mutations.
21 pathogenic mutations in the USH2A gene have been identified in 11 Chinese families by using the targeted next-generation sequencing (NGS) technology. We identified 21 pathogenic mutations, of which 13, including 5 associated with RP and 8 with USH II, have not be been previously reported. Visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations. These findings provide a basis for investigating genotype-phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.
What this means for Usher syndrome: This study provides additional genetic information about Usher syndrome type 2.
Mojo, a startup company, has recently developed a contact lens that can be used like a smartphone. The goal is to develop lenses that show you a menu and options when you want them and hide them when you don’t. These lens would not only be functional with smart options, but could also be fitted with a patients prescription. The goal of these lenses is to provide assistance in mobility and reading for those with poor vision. The clinic trials of these lenses will take place in Palo Alta at the Vista Center for the Blind and Visually Impaired and will be focus on patients who suffer from retinitis pigmentosa and macular degeneration.
What this means for Usher syndrome: These devices may be able to assist patients with Usher syndrome.
The aim of this study is to determine if umbilical cord Wharton’s jelly derived mesenchymal stem cells implanted in sub-tenon space have beneficial effects on visual functions in RP patients by reactivating the degenerated photoreceptors in dormant phase. 32 RP patients participated in the study and were followed for 6 months after the Wharton’s jelly derived mesenchymal stem cell administration. Regardless of the type of genetic mutation, sub-tenon Wharton's jelly derived mesenchymal stem cell administration appears to be an effective and safe option. There are no serious adverse events or ophthalmic / systemic side effects for 6 months follow-up. Although the long-term adverse effects are still unknown, as an extraocular approach, subtenon implantation of the stem cells seems to be a reasonable way to avoid the devastating side effects of intravitreal/submacular injection.
What this means for Usher syndrome: If successful, this stem cell therapy will help Usher patients to recover their vision while minimizing the invasive adverse effects of the treatment.
Researchers at the University of New Hampshire have reported the first structural model for a key enzyme, PDE6, and its activating protein that play a role in some genetically inherited eye diseases, such as retinitis pigmentosa and night blindness. Creating atomic-level models is important for locating PDE6 mutations because we can learn to understand why they cause disease and develop new therapeutic interventions to manage retinal diseases. Michael Irwin, doctoral student in biochemistry stated, “Having detailed structural information about how PDE6 is activated by transduction will help us understand the molecular causes of visual disorders and blinding diseases resulting from mutations in these proteins.” Current treatments for genetically inherited retinal diseases may include gene therapy or drugs meant to inhibit the disease process. However, the drugs are not always successful in restoring the balance of PDE6 and preventing blindness.
What this means for Usher syndrome: By knowing the molecular structure of these visual signaling proteins and how they interact with each other can offer clues for the development of new drugs to restore vision and prevent blindness.
Excitotoxicity is a process in which neurons are damaged and killed due to excessive amounts of a specific amino acid, glutamate (Glu). This process appears to play a critical role in ocular neurodegeneration by causing retinal ganglion cell death and cell loss. Uncontrolled glutamate in the synapsis has significant implications in the pathogenesis of neurogenerative disorders. Approaches to control the level of glutamate include targeting neural tissue to protect from degradation, and microparticles are often used as a vehicle for targeted drug delivery due to their ability to maintain stable drug concentration for prolonged periods. They can even help increase efficacy by improving drug bioavailability (the ability of a drug to be absorbed and utilized by the body). Based on promising results, possible new investigations will focus heavily on microparticulate formulations and can be expected to open the field of ocular research to new alternatives.
What this means for Usher syndrome: Retinitis pigmentosa is an eye-disease that is characterized by progressive retinal degeneration. The promising utility of microparticulates may one day be used to deliver therapeutic drugs as a potential treatment for Usher syndrome.
When Kevin Booth started his thesis at the University of Iowa, there were 10 genes linked to Usher syndrome, including the CIB2 gene (USH1J). Interested in understanding whether mutations in the CIB2 gene cause Usher, he started his investigation in the Molecular Otolaryngology and Renal Research Laboratory with Professor Richard J. Smith. Working with clinicians and collaborators, Booth identified and examined the results of thousands of patients with the CIB2 mutation. The in-depth examinations revealed that patients had perfectly healthy retinas and no balance issues but the genetic evidence refuting CIB2’s role in Usher syndrome was not enough for Booth. Along with a team of scientists from the Institut Pasteur in Paris, Booth utilized a comprehensive approach, which included phenotyping, cutting edge genomic technologies, murine mutant models, and functional assays, that showed mutations in CIB2 do not cause Usher syndrome.
What this means for Usher Syndrome: This means that CIB2 does not cause Usher syndrome and USH1J is no longer considered a subtype of Usher syndrome. Parents of deaf children with mutations in CIB2 will no longer be told that their child will also develop retinitis pigmentosa. The counseling that these families will receive after the genetic results will change accordingly.
Researchers at the National Eye Institute are launching a clinical trial to test the safety of a novel patient-specific stem cell-based therapy to treat geographic atrophy, the advanced “dry” form of age-related macular degeneration (AMD), a leading cause of vision loss among people age 65 and older. This is the first clinical trial in the USA to utilize replacement tissues from patient-derived induced pluripotent stem cells (iPSC). Under the phase I/IIa clinical trial protocol, 12 patients with advanced-stage geographic atrophy will receive the iPSC-derived RPE implant in one of their eyes. The patients will be closely monitored for at least one year to confirm safety.
What this means for Usher syndrome: This trial could pave the way to stem cell treatments of other eye diseases, including Usher syndrome.
Neuroscientists at Lund University in Sweden have developed a new technology that engineers the shell of a virus to deliver gene therapy to the precise cell type that needs to be treated. According to neuroscientist Tomas Björklund, “Thanks to this technology, we can study millions of new virus variants in cell culture and animal models simultaneously. From this, we can subsequently create a computer simulation that constructs the most suitable virus shell for the chosen application.” With this new method, researchers have been able to reduce the need for laboratory animals significantly because millions of the variants of the same drug are studied in the same individual. Additionally, they have been able to move important parts of the study from animals to cultured human stem cells.
What this means for Usher syndrome: This study provides potential methods to deliver genes effectively to the appropriate cells required for vision.
The identification of genetic defects that underlie inherited retinal diseases (IRDs) paves the way for the development of therapeutic strategies. Nonsense mutations result in a premature termination codon (PTC) and cause approximately 12% of all IRD cases. An approach that targets nonsense mutations could be a promising pharmacogenetic strategy for the treatment of IRDs. We provide novel data on the read-through efficacy of Ataluren, a translational read-through inducing drug (TRID), on a nonsense mutation in the Usher syndrome gene USH2A that causes deafblindness in humans. We validated Ataluren's efficacy to induce read-through on a nonsense mutation in USH2A-related IRD. Our findings support the use of patient-derived fibroblasts as a platform for the validation of preclinical therapies.
What this means for Usher syndrome:This study tests a potential therapy that could be used to treat Usher syndrome patients who have nonsense mutations.
How do you cope with living with Usher syndrome? What strategies do you use to overcome challenges? In this USH Talk, Dr. Moa Wahlqvist summarizes the findings from the first qualitative scientific study of its kind, exploring the strategies described by 14 people with Usher syndrome type 2 seeking to remain active agents in their own lives.
Inherited retinal dystrophies (IRDs) are characterized by progressive photoreceptor degeneration and vision loss. Usher syndrome (USH) is a syndromic IRD characterized by retinitis pigmentosa (RP) and hearing loss. USH is clinically and genetically heterogeneous, and the most prevalent causative gene is USH2A. USH2A mutations also account for a large number of isolated autosomal recessive RP (arRP) cases. This high prevalence is due to two recurrent USH2A mutations, c.2276G>T and c.2299delG. Due to the large size of the USH2A cDNA, gene augmentation therapy is inaccessible. However, CRISPR/Cas9-mediated genome editing is a viable alternative. We used enhanced specificity Cas9 of Streptococcus pyogenes (eSpCas9) to successfully achieve seamless correction of the two most prevalent USH2A mutations in induced pluripotent stem cells (iPSCs) of patients with USH or arRP. Our results highlight features that promote high target efficacy and specificity of eSpCas9. Consistently, we did not identify any off-target mutagenesis in the corrected iPSCs, which also retained pluripotency and genetic stability. Furthermore, analysis of USH2A expression unexpectedly identified aberrant mRNA levels associated with the c.2276G>T and c.2299delG mutations that were reverted following correction. Taken together, our efficient CRISPR/Cas9-mediated strategy for USH2A mutation correction brings hope for a potential treatment for USH and arRP patients.
What this means for Usher syndrome: Although still in its initial steps, the implementation of this type of strategy will people with Usher the possibility of replacing the defective photoreceptors with their own corrected ones. This will be especially relevant for those patients carrying mutations in some of the largest genes.
Cedars-Sinai, a non-profit healthcare organization based in Los Angeles, has received authorization from the FDA to launch a 16-person, Phase 1/2a clinical trial of human neural progenitor cells—stem cells that have almost developed into neural cells—for patients with retinitis pigmentosa (RP). The trial will be launched after investigators receive the final institutional review of the study protocol. The trial is being funded by a $10.5 million grant from the California Institute for Regenerative Medicine. The initial study was conducted by Dr. Shaomei Wang, MD, PhD, a professor of Biomedical Sciences and a research scientist in the Eye Program at the Board of Governors Regenerative Medicine Institute. He showed that human neural progenitor cells have the potential to treat RP. The clinical trial will be directed by Dr. Clive Svendsen, PhD, professor of Biomedical Sciences and Medicine and director the Cedars-Sinai Board of Governors Regenerative Medicine Institute. Dr. David Lao, MD, from Retina-Vitreous Associates Medical Group in Beverly Hill, will be responsible for the subretinal injection of the cells into patients. The ultimate goal of this therapy is to restore the vision by replacing the defective photoreceptors.
What this means for Usher syndrome: This means that more potential stem-cell based treatments are becoming available to treat Usher patients. Since photoreceptors are the main cell group affected in Usher syndrome, the possibility of successfully replacing them with healthy cells give hope to patients that are losing their sight. Still we need to be careful and wait for the results of this new clinical trial.
Retinitis Pigmentosa targets the rod and cone photoreceptor cells, but the disease does minimal damage to the retina’s many other neurons, which “process signals from the rods and cones and convey the results to the optic nerve.” One way to restore vision is to replace the damaged photoreceptors with a device that generates electrical pulses in response to light. Through the various points on the device, pulses can communicate with the retina’s surviving neurons in a natural way. Lanzani and colleagues at IIT are investigating a new kind of retinal prosthesis made from semi-conductive polymers, a class of carbon-based plastics that can conduct electricity in the same way that silicon microchips do.
What this means for Usher syndrome: Researchers are developing new types of prosthetics that will replace damaged photoreceptors and potentially restore vision for those with RP.
This study used the highly sensitive RNAscope in situ hybridization assay and single-cell RNA-sequencing techniques to investigate the distribution of Clrn1 and CLRN1 in mouse and human retina respectively. The pattern of Clrn1 mRNA cellular expression is similar in both mouse and adult human retina, with CLRN1 transcription being localized in Müller glia and photoreceptors. The study generated a novel knock-in mouse with a hemagglutinin (HA) epitope-tagged CLRN1 and showed that CLRN1 is expressed continuously at the protein level in the retina. Following enzymatic de-glycosylation and immunoblotting analysis, scientists detected a single CLRN1-specific protein band in homogenates of mouse and human retina, consistent in size with the main CLRN1 isoform. Taken together, their results implicate Müller glia in USH3 pathology, for future mechanistic and therapeutic studies to prevent vision loss in this disease.
What this means for Usher syndrome: As shown in previous studies of the USH1C protein in zebrafish, Müller glia, in addition to photoreceptors, may be involved in Usher syndrome.
Pamela Aasen, the proud parent of Ethan & Gavin who have Usher syndrome type 1b, reflects on her family's journey to overcome the challenges of Usher syndrome.
Megan Lengel, a recent college graduate and young adult with Usher syndrome, has offered to share with us her valuable experience attending college while dealing with Usher syndrome.
Wake Forest Institute for Regenerative Medicine (WFIRM) scientists have fine-tuned their delivery system to send a DNA editing tool to alter DNA sequences and modify gene function. With this new method, researchers can package together the Cas9 protein and guide RNA for the CRISPR mediated gene editing. Previously, the two components—Cas9 protein and guide RNA—had to be delivered separately which was not as efficient. The new system offers the delivery efficiency of conventional lentiviral vectors that enable transient Cas9 expression. Transient Cas9 expression means a decrease chance of having unwanted effects when using this therapy.
What this means for Usher syndrome: For Usher patients, improving the efficacy of CRISPR technology means that they will be able to receive a more efficient treatment with very low side-effects.
Case Western Reserve University (CWRU) and Boston-based genetic medicine company Akouos have entered into an exclusive licensing agreement to develop a patented gene therapy that could potentially treat hearing loss associated with a type of Usher syndrome. It may be able to stop the progression of hearing loss and prevent deafness in people with USH3A. The hearing loss is “sensorineural,” meaning it is caused by abnormalities of the inner ear, while the vision is due to the degeneration of the retina at the back of the eye. The technology has allowed researchers to develop a more precise animal model of the hearing loss associated with Usher syndrome type 3A, and the potential for the technology to deliver the preservation of hearing and quality of life for children and adults diagnosed with the genetic disorder.
What this means for Usher syndrome: The development of a more precise animal model for USH3A will exponentially expedite the identification of novel and more efficient therapies to slow or complete stop the progression of this disease.
Currently, there are no studies on life strategies in people with Usher syndrome and people with deafblindness are often described in terms of poor health and low quality of life. From a clinical standpoint, it is important to balance this picture with an increased knowledge of life strategies. Fourteen people between the ages of 20 to 64 years with USH2A in Sweden participated in focus group interviews, which were transcribed and analyzed by qualitative content analysis. The findings show that people with USH2A have a variety of life strategies that can be interpreted as highlighting different aspects of psychological flexibility in a life adjustment process. The study demonstrates that people with USH2A manage in many ways, and metaphorically, by “taking the helm,” they strive to actively navigate towards their own chosen values.
What this means for Usher syndrome: More studies like the one described here will help Usher patients to look for strategies to cope with this disease and improve their quality of life.
As part of the Human Cell Atlas Project, Australian scientists created the world’s most detailed gene map of the human retina. Dr. Wong says, “By creating a genetic map of the human retina, we can understand the factors that enable cells to keep functioning and contribute to healthy vision.” The map provides a detailed gene profile of individual retinal cell types that will help us study how those genes impact different kinds of cells. Scientists can have a clear benchmark to assess the quality of the cells derived from stem cells to determine whether they have the correct genetic code which will enable them to function.
What this means for Usher syndrome: By having this atlas of healthy cells and their interconnections, researchers will be able to predict the effect of different drugs to treat eye diseases, including Usher syndrome.
Researchers in Germany have recently developed a “retina-on-a-chip” which combines living human cells with an artificial tissue-like system. The scientists describe their work as “merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human Retina-on-a-Chip platform.” Ophthalmologic drugs largely rely on animal models, which often do not provide results that are translatable to human patients. In this study, researchers present the retina-on-a-chip (RoC), a novel microphysiological model of the human retina integrating more than seven different essential retinal cell-types derived from human induced pluripotent stem cells (hiPSCs).
What this means for Usher syndrome: this model can be used to test hundreds of drugs for harmful effects on the “human” retina very quickly and enables scientists to take stem cells from a specific patient and study both the disease and potential treatment in the individual’s own cells.
CRISPR (clustered regularly interspaced palindromic repeats) is a cutting-edge genetic editing technique that enables the targeting and editing of specific sequences in the human DNA. CRISPR is known to result in unwanted gene edits that can occur when working with embryos. However, if the edits are done on adult humans and children, no transference occurs, and any potential damage remains to one individual. Allergan and Editas Medicine EDIT, a pharmaceutical company in Cambridge, Massachusetts, has announced in July they are ready to enroll subjects into its first of its kind CRISPR-based therapy trials, a development that would involve gene editing inside the human body. A propriety EDIT-101 injection is administrated into the eye to deliver “gene-altering machinery” directly to the photoreceptor cells. Once injected, EDIT-101 cuts out the mutated DNA, including CEP290 gene responsible for progressive photoreceptor-cell loss, which leads to an inherited type of blindness, Leber congenital amaurosis 10. The goal is for this cut to be repair by the DNA-repairing process that will lead to the expression of the normal protein.
What this means for Usher syndrome: potential treatments for vision loss are being discovered every day. In this case, the use of CRISPR technology will help to replace and repair mutations present in the Usher proteins and thus, help to restore vision as well as hearing.
In a new study of patients with Retinitis Pigmentosa, the Keck School of Medicine of USC researchers have found that adapted augmented reality (AR) glasses can improve patients’ mobility by 50% and grasp performance by 70%. Utilizing a different approach by employing assistive technology to enhance natural senses, the team adapted AR glasses that project bright colors onto patients’ retinas, corresponding to nearby obstacles.
What this means for Usher syndrome: we can improve the quality of life for patients with low vision due to retinitis pigmentosa through the use of augmented reality technology.
Drug repurposing is a new and attractive aspect of therapy development that could offer low-cost and accelerated establishment of new treatment options. The enzyme poly-ADP-ribose-polymerase (PARP) has important roles for many forms of DNA repair and it also participates in transcription, chromatin remodeling and cell death signaling. Currently, some PARP inhibitors are approved for cancer therapy, by means of canceling DNA repair processes and cell division.
Excessive PARP activity is also involved in neurodegenerative diseases including the currently untreatable and blinding retinitis pigmentosa group of inherited retinal photoreceptor degenerations. Hence, repurposing of known PARP inhibitors for patients with non-oncological diseases might provide a facilitated route for a novel retinitis pigmentosa therapy.
What this means for Usher syndrome: PARP inhibitors are approved for their use in cancer therapy, suggesting they can be repurposed to treat retinitis pigmentosa at a very low cost and shorter waiting times compared to novel drugs.
To develop biological approaches to restore vision, scientists developed a method of transplanting stem cell-derived retinal tissue into the retina of an animal model, a cat. Human embryonic stem cells were successfully grafted into the retina of cats. The researchers observed strong infiltration of immune cells into the graft and surrounding tissue in the cats treated with prednisolone alone. The cats treated with prednisolone plus cyclosporine A showed better survival and low immune response to the grafts. This work demonstrates the feasibility of engrafting human embryonic stem cell-derived retinal tissue into the retina of large-eye animal models. Transplanting retinal tissue in degenerating cat retina will enable rapid development of preclinical work focused on vision restoration.
What this means for Usher syndrome: This procedure may provide a platform for testing stem cell-based therapies to treat Usher syndrome patients.
Scientists from Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland and Scuola Superiore Sant’ Anna in Italy are developing a technology, OpticSELINE, for the blind that stimulates the optic nerve. The idea is to produce phosphenes, the sensation of seeing light in the form of seeing white patterns, without seeing light directly. Unfortunately, only a few hundred patients qualify for the current retinal implants on the market for clinical reasons. The intraneural electrode is a potential solution to this exclusion, since the optic nerve and the pathway to the brain are often intact. Intraneural electrodes contain an array of 12 electrodes and are more stable and less likely to move around once they are implanted. To understand the effectiveness of the electrodes, scientists delivered electric current to the optic nerve through OpticSELINE and measured the brain’s activity . The stimulation showed each electrode induces a special pattern of cortical activation, suggesting that intraneural stimulation of the optic nerve is selective and informative.
What this means for Usher syndrome: newer technologies such as the OpticSELINE are being developed as potential solutions to help the blind see. It might take some time and several clinical trials to fine-tune those stimulated cortical patterns but as they are now those visual signals generated by the OpticSELINE will be able to provide visual aid in the near future.
The identification of the causes and understandings of the functions of many inherited retinal diseases (IRDs) has led to the development of exciting new gene/disease specific treatment opportunities. There are numerous treatments available that are aimed at a level of not just targeting specific genes but also certain mutations. Therefore, gene/disease specific treatments rely on persistent target cells and sufficient visual function to work effectively. However, many patients are outside of this window of opportunity and must rely on other approaches.
What this means for Usher syndrome: there are many different treatment and therapy options that are in development for retinitis pigmentosa.
Usher syndrome (USH) is the most common cause of inherited deaf-blindness. Currently there is no therapy for vision loss caused by USH. Rodents have been used as animal models for USH but even with defects in their USH genes, they do not often exhibit the vision loss humans experience. The lack of animal models that share human characteristics of USH makes it difficult to study the protein and any possible therapeutic interventions. In this study, researchers were able to modify the USH1C gene in pigs. They did this by copying the human USH1C gene with the mutation using bacterial recombineering into the pig genome. Through this, researchers were able to create USH1C piglets that are born deaf and have vestibular dysfunctions. Behavioral tests also showed a reduction in vision. This is the first time researchers have created a large animal model for USH1.
What this means for Usher syndrome: Researchers now have a functioning animal model of USH1C that they can use to study the USH1C gene and possible therapies. This allows further research to be conducted for cures for USH.
Researchers at Children’s Hospital of Philadelphia (CHOP) reported a more sensitive method for capturing the footprint of AAV vectors — the range of sites where the vectors transfer new genetic material. AAV vectors are bioengineered tools that use a harmless virus to transport modified genetic material safely into tissues and cells. To use these vectors safely and effectively, researchers must have a complete picture of where in the body the virus delivers the gene. Current methods to define gene transfer rely on fluorescent reporter genes that glow under a microscope, highlighting cells that take up and express the delivered genetic material. Unfortunately, these methods reveal only cells with stable, high levels of cargo. This new technology provides a better and more sensitive method for researchers to detect where the gene is expressed, even if it is expressed at low levels or for only a short time. To address this gap, Beverly L. Davidson, PhD and her laboratory developed a new AAV screening technique that uses sensitive editing-reporter transgenic mice that are marked even with a short burst of expression.
What this means for Usher syndrome: This new method will help to improve the safety of AAV-gene editing approaches because it better defines sites where the vector expresses the modified gene. AAV-gene editing might be developed into a treatment for Usher syndrome.
Scientists from Okayama University have developed a film coupled with photoelectric dye that generates electric signals in response to light. When the device was placed on an instrument that measures electric potential, the film generated waves of electric signals after being exposed to a flashing light. Researchers have highlighted that the device may function as a “novel type of retinal prosthesis.”
What this means for Usher syndrome: This device might be developed into an implant treatment for vision loss in Usher syndrome.
When a person becomes blind their brain’s visual cortex is typically undamaged, but it is not receiving information from the eyes. Six blind people have now had their vision partially restored thanks to Orion, a new device that feeds images from a camera directly into the brain. The Orion device has two main parts: a brain implant and a pair of glasses. The implant consists of sixty electrodes that receive information from a camera mounted on the glasses. Together, they deliver visual information to the brain; thus, bypassing the eye.
What this means for Usher syndrome: This system might provide vision in Usher syndrome patients who are completely blind.
“Researchers have developed a significantly improved delivery mechanism for the CRISPR/Cas9 gene editing method in the liver. The delivery uses biodegradable synthetic lipid nanoparticles that carry the molecular editing tools into the cell to alter the cells’ genetic code precisely with as much as 90 percent efficiency. The nanoparticles could help overcome technical hurdles to enable gene editing in a broad range of clinical therapeutic applications.”
What this means for Usher syndrome: This technique may provide a means for delivering gene therapies to the retina in Usher syndrome patients.
Researchers developed a mouse model with genetically defective rods that mimics developmental blindness disorders in humans. A team examined the structure of the defective retina, as well as its response to light with or without gene therapy. The rods that received gene therapy not only regained normal light response, but also recovered normal connections to other retinal neurons.
What this means for Usher syndrome: If future treatments for Usher syndrome can save photoreceptors from dying, the saved cells may be able to reconnect and become functional.
Kathy Thompson, Board Director of the Coalition, steps out of her comfort zone and goes camping.
Lane, a mother of two children with Usher Syndrome, writes about her experience at the Usher syndrome Coalition Annual Conference. She explains how these conferences have positively affected not just herself but her whole family.
OliX Pharmaceuticals Inc. in South Korea, a leading developer of RNAi therapeutics, is expanding its research in ocular diseases.
GenSight Biologics, a biopharma company focused on discovering and developing gene therapies for retinal neurodegenerative diseases and central nervous system disorders, announced that the independent Data Safety Monitoring Board (DSMB) has completed its first safety review of the ongoing PIONEER Phase I/II clinical trial of GS030 combining gene therapy and optogenetics for the treatment of Retinitis Pigmentosa (RP). No safety issues have been found for the first cohort of subjects who received a single intravitreal injection of 5e10 vg combined with a wearable optronic visual stimulation device. Therefore, the DSMB has recommended moving forward with the plan without any modification to the protocol and recruiting the second cohort of subjects to receive an escalated dose of 1.5e11 vg.
What this means for Usher syndrome: This clinical trial could lead to a treatment for RP and may be applicable to Usher syndrome.
Researchers have identified three new pathogenic variants in two Usher syndrome genes, USH2A and ADGRV1.
Eloxx Pharmaceuticals is developing small molecules that permit read-through of point mutations that cause Usher syndrome 1F and 2A. Eloxx has entered into a partnership with the Foundation Fighting Blindness and is developing molecules that “read through” nonsense mutations. Scientists believe that approximately 10% of all the gene mutations across all known inherited retinal diseases are nonsense. Therefore, the “read through” molecules have the potential to help many people.
What this means for Usher syndrome: A subset of Usher syndrome patients, those with nonsense mutations, might be helped by this therapy.
ReNeuron Group plc has announced the latest updated positive preliminary results in the company’s ongoing phase 1 and 2a clinical trial of its human retinal progenitor cell (hRPC) therapy candidate in retinitis pigmentosa. All three subjects in the first group of phase 2a have demonstrated a sustained and further improvement in vision compared to their pre-treatment baseline.
What this means for Usher syndrome: This potential therapy could provide a means to restore lost vision in Usher syndrome patients.
2Ctech Inc, a privately-held development stage company focused on the application of nanoparticle technologies for the treatment of retinal diseases, announced its first-known clinical program to demonstrate the effectiveness and safety of Quantum Dots (QDs) to achieve photovoltaic stimulation of the neural retina for preservation or enhancement of vision in patients with retinal degenerative diseases. QDs are semiconductor crystalline structures that absorb light and generate a dipole electrical field; thus, stimulating the neuronal retina cells. These particles are similar to solar cells, which produce energy in response to light. In the layers of the retina, the particle emissions are intended to result in direct stimulation of the neural retina, “creating action potentials that trigger the normal neural pathways to the brain.
What this means for Usher syndrome: This new technology holds promise to provide a means to restore lost vision in Usher syndrome patients.
Karen Andersen, Samira Kiani and their colleagues at Arizona State University described a method of rendering the CRISPR-Case9 gene-editing tool “immunosilent,” potentially allowing the editing and repair of genes to be accomplished reliably and without activating an immune response. Their study is the first to predict accurately the dominant binding sites or epitopes responsible for immune recognition of the Cas9 protein and experimentally target them for modification. These findings bring CRISPR a step closer to a safer clinical application.
What this means for Usher syndrome: This discovery could help pave the way toward FDA approval of CRISPR/Cas9 gene editing therapies to treat Usher syndrome.
Ophthotech has licensed exclusive rights to develop novel adeno-associated virus (AAV) gene therapy candidates for Best disease and other bestrophinopathies from University of Pennsylvania (Penn) and the University of Florida Research Foundation (UFRF). The agreement allowed Ophthotech to enter talks with Penn and UFRF to acquire a license for novel AAV serotype 2 based gene therapy product candidates for Best disease, an orphan inherited degenerative retinal disease caused by mutations in the BESTI gene. Additionally, Ophthotech says it expects to initiate a Phase I/II clinical trial for the Best disease candidate in the first half of 2021.
What this means for Usher syndrome: If the first clinical trials for Best disease using this novel AVV gene therapy are successful, this means Ophthotech will probably look for other eye-related diseases like Usher syndrome.
RNA, the short-lived cousin to its better-known partner, DNA, is the blueprint for protein production in cells. Joshua Rosenthal told researchers about how the squid and octopuses make prolific use of an enzyme called ADAR to catalyze thousands of single-letter changes to the RNA code. These minor edits alter the structure and activity of proteins that control electrical impulses in the animals’ nerves. Rosenthal’s studies on squids inspired him to hijack ADAR and program it for making precise edits to the human RNA. Additionally, the editing of RNA is reversible, since cells are constantly churning out new copies of RNA. If Rosenthal’s RNA editors work in humans, they could be used repeatedly to treat genetic diseases without confronting the unknown, long-term risks of permanent DNA editing with CRISPR.
What this means for Usher syndrome: Although too early to say, RNA-reversibly editing can develop in an alternative strategy for the repair of point mutations in Usher genes.
Researchers were able to evaluate the effect of Simvastatin, a drug used to treat high cholesterol and high triglyceride levels in the blood, on photoreceptors exposed to oxidative stress.
Adeno-associated viruses (AAV) engineered to target specific cells into the retina can be injected directly into the vitreous of the eye to deliver genes more precisely than with wild type AAVs, which must be injected directly under the retina. Researchers at the University of California, Berkeley inserted a gene for a green-light receptor into the eyes of blind mice, and a month later the mice could maneuver obstacles as easily as mice without visual impairments. The mice could use motion, brightness changes over time, and fine detail on an iPad.
What this means for Usher syndrome: Retinal delivery of AAV can always have the adverse effects of tissue inflammation and/or retinal detachment. This new strategy, delivering the modified virus into the vitreous, will prevent those side effects. For Usher patients, this means that, if successful, this therapy will increase the probability of success in restoring vision.
Stem cells are cells that have the capability of becoming any type of cells in an organism and in the right environment. Researchers are trying to use stem cell therapy to replace lost photoreceptors and preserve residual photoreceptors during retinal degeneration. One of the problems is that the degenerative microenvironment that already exists in the diseased retina compromises the fate of grafted cells. The desired donor cells will need to have both proper regenerative capability and the ability to improve their own microenvironment. For this purpose, the authors of the present work used specific cell surface molecules that help to kill tumorigenic embryonic cells and at the same time enrich retinal progenitor cells. The retinal progenitors were obtained from embryonic stem cells derived from retinal organoids (three dimensional structures derived from pluripotent cells) that were grafted into retinal degeneration rat and mouse models. After three months post-treatment, those animals showed a 40% increase in healthy photoreceptor cells and a decrease in inflammatory molecules, demonstrating the importance of a healthier environment for the grafted cells.
What this means for Usher syndrome: These two features of the organoid systems, regenerative capability and generation of a healthier microenvironment, will, very likely, benefit Usher patients as an additional therapy to delay or prevent photoreceptor loss.
Ganglion cells in the eye generate noise as the light-sensitive photoreceptors die in diseases such as retinitis pigmentosa (RP). Now, neurobiologists have found a drug and gene therapy that can tamp down the noise, improving sight in mice with RP. These therapies could potentially extend the period of useful vision in those with degenerative eye diseases, including, perhaps, age-related macular degeneration.
What this means for Usher syndrome: This type of therapy may also extend the period of useful vision in Usher syndrome.
ProQR Therapeutics N.V., a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, today announced the first patient treated in the Phase 1/2 STELLAR clinical trial for QR-421a in patients with Usher syndrome type 2 or non-syndromic retinitis pigmentosa (RP). Interim data from the trial are expected to be announced by mid-2019. According to David G. Birch, Ph.D., Principal Investigator of STELLAR and Scientific Director of the Retina Foundation of the Southwest in Dallas, Texas, “The STELLAR study is one of the first studies of its kind exploring the impact of ProQR’s RNA therapies on patients with Usher syndrome type 2 due to an Exon 13 mutation. The STELLAR trial will explore whether QR-421a (ProQR’s RNA therapy) can slow disease progression or even reverse it.”
What this means for Usher syndrome: There may be a potential drug available to reverse blindness caused by Usher syndrome.
ReNeuron Group, a UK-based global leader in the development of cell-based therapeutics, announced positive preliminary results in the company’s ongoing Phase 1/2 clinical trial of its human retinal progenitor cells candidate therapy for the blindness-causing disease, retinitis pigmentosa (RP). All three subjects in the first group of the Phase 2 part of the trial demonstrated a significant improvement in vision at the follow-up compared to their pre-treatment baseline and compared with their untreated control eye.
What this means for Usher syndrome: A similar cell-based therapy tailored to Usher syndrome may help restore vision.
A team of scientists from Sechenov First Moscow State Medical University (MSMU), together with colleagues from leading scientific centers in India and Moscow, described several genetic mutations causing Usher syndrome.
What this means for Usher syndrome: These previously unstudied genetic mutations will allow us to identify new targets for specific therapies.
The United States Patent & Trademark Office (USPTO) has approved the usage of mesencephalic-astrocyte-derived neurotrophic factor (MANF) or cerebral dopamine neurotropic factor (CDNF) as a treatment for various retinal disorders including retinitis pigmentosa, macular degeneration, or glaucoma. Both factors can be administered as an eye drop or by intravitreal injection. MANF is believed to have potential because it is a naturally-occurring protein produced by the body to reduce or prevent cell death in response to injury or disease through unfolded protein response.
What this means for Usher syndrome: Since MANF reduces or prevents cell death, in the case of Usher syndrome, it could prevent photoreceptor cells from dying, and thus preserve vision.
In this study, we proposed a new method for evaluating the results based on the sizes of the phosphenes that the patient drew. Additionally, we described the methodology of psychological testing and support for a deaf-blind patient. The patient with the retinal prosthesis, Argus II, felt more independent, confident, and healthier.
What this means for Usher syndrome: The results of this study provide a better understanding of retinal implants for patients with vision loss.
A new purple protein, bacteriorhodopsin, has made its way from a tiny laboratory in Farmington, Connecticut, all the way up to the International Space Station. Since bacteriorhodopsin is light-sensitive, researchers hope to implant it into human eyes. The thought is that the protein could be used to replace cells that die due to diseases like retinitis pigmentosa and age-related macular degeneration. To simulate the cells, the laboratory in Farmington needs to build what it is called “organic implants” by layering the bacteriorhodopsin onto a film and dipping it over and over into a series of solutions. These solutions need to have a uniform distribution that can be adversely affected by gravity. To test this, LambdaVision has secured a spot for their experiment aboard the International Space Station, using funding from the ISS National Lab and Boeing.
What this means for Usher syndrome: These “organic implants”, composed of bacteriorhodopsin, could be capable of replacing dying photoreceptors in the retina.
To describe the genetic and phenotypic spectrum of Usher syndrome after 6 years of studies by next-generation sequencing, researchers propose an up-to-date classification of Usher genes in patients. The systematic review and meta-analysis protocol were based on the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Researchers performed (1) a meta-analysis of data from 11 next-generation sequencing studies in patients with Usher syndrome and (2) a meta-analysis of data from 21 next-generation studies in 2,476 patients to assess the involvement of Usher genes in nonsyndromic hearing loss, and then 3) a statistical analysis of the differences between parts 1 and 2. The new findings provide evidence that Usher protein dysfunction is the second cause of genetic sensorineural hearing loss after connexin dysfunction.
What this means for Usher syndrome: These results will promote the inclusion of early genetic screening for all the Usher genes in deaf children and also it will help to establish the proportion of patients that will be at high-risk of developing retinitis pigmentosa.
Researchers revealed that culturing human induced pluripotent stem cells with different isoforms of the extracellular component laminin led to the creation of cells specific to different parts of the eye, including retinal, corneal, and neural crest cells. They showed that the different laminin variants affected the cells' motility, density, and interactions, resulting in their differentiation into specific ocular cell lineages. Cells cultured in this way could be used to treat various ocular diseases.
What this means for Usher syndrome: There is the possibility of replacing the photoreceptor cells that are dying in the retina with pluripotent cells that have been grown and induced into healthy photoreceptor cells.
Scientists at the Francis Crick Institute have discovered a set of simple rules that can determine the precision of CRISPR/Cas9 genome editing in human cells. These rules could help to improve the efficiency and safety of genome editing in both the lab and the clinic. By examining the effect of CRISPR genome editing at 1491 target sites across 450 genes in human cells, the team have discovered that the outcomes can be predicted based on simple rules. In this study, researchers have found that the outcome of a particular gene edit depends on the fourth letter from the end of the RNA guide, synthetic molecules made up of about 20 genetic letters (A, T, C, G). “The team discovered that if this letter is an A or a T, there will be a very precise genetic insertion; a C will lead to a relatively precise deletion and a G will lead to many imprecise deletions. Thus, simply avoiding sites containing a G makes genome editing much more predictable.”
What this means for Usher syndrome: Scientists will theoretically be able to repair the mutation present in an Usher gene by selecting the correct genetic letter from the end of the RNA guide.
ProQR Therapeutics announced that the FDA has cleared the Investigational New Drug (IND) application for QR-421a. QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of the vision loss associated with Usher syndrome type 2 and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. ProQR plans to start enrolling patients in a Phase 1/2 trial named STELLAR in the coming months with preliminary data expected in mid-2019.
We are pleased to share with you the video, transcripts, slides and summaries of the 2018 International Symposium on Usher Syndrome in Mainz, Germany.
The light scalpel has the potential of preventing the “ripple effect” that occurs following a trigger that leads to glaucoma or macular degeneration. By utilizing the femtosecond laser, small holes appear in the cells of the eye’s retina, making it possible to effectively inject drugs or genes in specific areas of the eye. The key feature of this technology is extreme precision because through the usage of gold nanoparticles, the light scalpel makes it possible to precisely locate the family of cells where the doctor will have to intervene.
What this means for Usher syndrome: In CRISPR/Cas9 editing or drug delivery, the utilization of the femtosecond laser will improve the delivery of the specific compound to the affected area with minimum side effects.
In August, it will be a year since the first commercial IRIS®II retinal chip implantation in Europe took place; it has allowed a blind patient to perceive light stimuli and use it to locate objects, meaning that she can be more independent. This work has made it possible to integrate artificial vision technology, which includes an electrical retinal stimulator with over 150 electrodes, glasses with a bio-inspired mini-camera and a pocket processor into this patient’s day-to-day life. For the patient, blind from a result of retinitis pigmentosa, the retinal chip is another way of supporting her in her daily life, together with her guide dog and the use of a cane.
What this means for Usher syndrome: There are possible technologies available to help the blind live and navigate independently.
Hans Jørgen Wiberg describes Be My Eyes, the app made up of a global community that connects people who are blind or have low vision with sighted volunteers from around the world through a live video call.
Since 1995, University of California, Irvine stem cell researcher Magdalene J. Seiler, PhD has pursued promising research into the development and usage of retinal sheet transplantation. The treatment is based on transplanting sheets of stem cell-derived retina, called retina organoids to the back of the eye with hopes of re-establishing the neural circuity within the eye. Recently, Seiler has received a $4.8 million grant from the California Institute of Regenerative Medicine (CIRM) to continue to develop a stem cell-based therapy for retinal diseases such as retinitis pigmentosa.
A group of research physicians have discovered that using stem cells from a person’s own bone marrow has reported success in improving vision for patients with Retinitis Pigmentosa. The bone marrow stem cells come from the same person; therefore, there can be no rejection. Of the 33 eyes studied, 45.5% of individual eyes improved and 45.5% remained stable over the follow-up period when they typically have been worsening. Vision improvement is 98.4% likely to be a consequence of this treatment.
A US clinician has received a five-year £6.1 million grant to investigate the potential of advancing a gene therapy currently used in dogs to help retinitis pigmentosa (RP) patients. The treatment restored the night vision and stopped the progression of the daytime vision-loss in dogs with progressive retinal atrophy (PRA). PRA is an inherited condition in dogs and is caused by the same genes that are responsible for RP. This new grant will allow clinicians to build on primary studies in preparation for a possible clinical trial in human patients with RP.
Scott Davert had the pleasure of attending the first Deaf-Blind International Conference for the Network of the Americas. The conference introduced a variety of technologies such as insideONE Tactile Braille Tablet, Captel, and Video Relay Services. Each of these technologies were designed to help deaf-blind people.
Sparing Vision, a French biotech, plans to use a naturally occurring protein called rod-derived cone-viability factor, which binds to a peptide on cone photoreceptor cells in the retina and allows more glucose to enter the cell. By allowing more glucose in, it will slow down or prevent cell death; thus stopping vision loss. This could be beneficial for patients with retinitis pigmentosa.
The nonprofit biomedical institute is seeking to acquire samples of every drug ever developed to see if they can be used to treat diseases besides those for which they were intended. That means collecting roughly 10,000 to 11,000 compounds discovered since the end of the 19th century. Most never made it to market, often because they weren’t effective or had unexpected side effects.
ProQR Therapeutics N.V. announced the results for their clinical trial of QR-110 LCA 10 is on track, and eight out of twelve patients have been enrolled in a Phase 1/2 trial. The results for safety and efficacy for the trial are expected to be announced in the second half of 2018. Currently, they planing to announce data from a QR-421 study for Usher Syndrome. The organization has received $7.5 million in funding from the Foundation Fighting Blindness (FFB) and hopes to use QR-421a for Usher Syndrome Type 2A to target mutations in exon 13.
For the last couple years, Ophthalmologist Dr. Kang Zhang and UC San Diego researchers have been working with CRISPR by injecting it into the eyes of mice with Retinitis Pigmentosa. According to Dr. Zhang, they have been able to bring back 30 percent of vision and sometimes 50 percent of vision. Zhang’s lab has recently received the green light to start clinical trials this fall and if the trial goes well then CRISPR can be applied to all human genetic diseases or conditions.
Researchers at Duke University believe they have developed an approach to treat retinal conditions such as Retinitis Pigmentosa, which include misfolded proteins in the cell that the eye cannot process. Scientists have shown by boosting the cells’ ability to process misfolded proteins could keep them from clustering inside the cell. They created and tested the strategy in mice, significantly delaying the onset of blindness. This technique would not be used to prevent cell death retinal diseases but also neurodegenerative diseases such as Huntington’s, Parkinson’s, and Alzheimer’s.
David Rand, Marie Jakešová, Gur Lubin, Ieva Vėbraitė, Moshe David-Pur, Vedran Đerek, Tobias Cramer, Niyazi Serdar Sariciftci, Yael Hanein, Eric Daniel Głowacki
A simple retinal prosthesis is being developed in collaboration between Tel Aviv University in Israel and Linköping University in Sweden. Fabricated using cheap and widely-available organic pigments used in printing inks and cosmetics, it consists of tiny pixels like a digital camera sensor on a nanometric scale. Researchers hope that it can restore sight to blind people.
Ekaterina S. Lobanova, Stella Finkelstein, Jing Li, Amanda M. Travis, Ying Hao, Mikael Klingeborn, Nikolai P. Skiba, Raymond J. Deshaies, Vadim Y. Arshavsky
New research outlines a strategy that in mouse models significantly delayed the onset of blindness from inherited retinal degeneration such as retinitis pigmentosa.
Bill Whitaker of CBS’s 60 minutes interviewed Feng Zeng to learn more about Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). Whitaker’s interview with Zhang provides basic facts that are accessible to anyone on CRISPR and its possibility of not only curing genetic diseases but preventing them altogether.
An Ottawa-based company, iBionics, is working to improve the effectiveness of vision-restoring technology by developing a bionic retina, the Diamond Eye implant. iBionics is targeting for full approval and commercial availability by 2024.
One of these recent discoveries doesn't replace an entire eye, but supplants a major component of vision. It holds some promise for millions of people who could otherwise go blind. In a first, scientists in China have created artificial photoreceptors to help blind mice see.
ReNeuron, a developer of cell-based therapeutics, received a $1.5 million grant award from the UK Innovations agency. The project will allow further development of cell banks of ReNeuron’s hRPC candidate and as well as the development of product release assays for late-stage clinical development. The hRPC therapy is currently being tested in a Phase III clinical trial in the US for patients suffering retinitis pigmentosa.
A retinal implant allowed a 69 year old woman with macular degeneration to see more than double the usual number of letters on the vision chart. Luxturna, the gene therapy was approved by the FDA in 2017, corrects a mutation found in Leber congential amaurosis (LCA).
Caroline C. W. Klaver, MD, PhD; Alberta A. H. J. Thiadens, MD, PhD
Children with retinitis pigmentosa who received vitamin A supplementation were associated with slower rate of cone electroretinogram amplitude compared to children who did not, a small study found.
This story is designed to help you find an answer to the question: will a stem cell therapy work for me? To get an answer, Dr. Mary Sunderland of the Foundation Fighting Blindness Canada, suggests that you pay attention to three key points when you read new stories about stem cell discoveries or clinical trials...
Rajiv Gandhi Govindaraj, Misagh Naderi, Manali Singha, Jeffrey Lemoine, Michal Brylinski
Researchers at the LSU Computational Systems Biology group have developed a sophisticated and systematic way to identify existing drugs that can be repositioned to treat a rare disease or condition. They have fine-tuned a computer-assisted drug repositioning process that can save time and money in helping these patients receive effective treatment.
Odylia Therapeutics aims to advance gene therapies that are getting left behind. Odylia’s focus is gene therapies with scientific promise but limited commercial opportunity that maybe gathering dust on the selves of labs or companies.
Three blind mice could be a thing of the past. Scientists have restored the sight of blind mice by implanting tiny gold prosthetic photoreceptors into their eyes. So far, this incredible technique has only been carried out on mice. However, the work holds some hope for people with degenerative eye diseases such as retinitis pigmentosa or macular degeneration.
Pixium Vision, a company developing innovative bionic vision systems to enable patients who have lost their sight to lead more independent lives, announces today the world’s first successful human implantation and activation of PRIMA, its new generation miniaturized wireless photovoltaic sub-retinal implant, in a patient with severe vision loss from atrophic dry Age-related Macular Degeneration (AMD).
A French biopharma company has announced their plans to carry out human trials of a new treatment that would insert genes from light-seeking algae into the eyes of patients with inherited blindness in order to help them regain sight. The treatment involves optogenetics, a technique that converts nerve cells into light sensitive cells.
GenSight will start a clinical trial in the UK testing a combination of gene therapy and a wearable device to restore sight in patients with retinitis pigmentosa. The Phase I and II trial, PIONEER, will study the safety and tolerability of GenSight’s therapy called GS030, in patients with end-stage retinitis pigmentosa with vision not better than “counting fingers.” The first patient will be tested in the first quarter of 2018 and outcomes will be measured after a year.
What this means for Usher syndrome: If GenSight’s therapy succeeds, it will very likely be tested in other diseases such as Usher syndrome.
GenSight Biologics, a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, announced UK Medicines and Healthcare Regulatory Agency (MHRA) acceptance of the Company’s Clinical Trial Application (CTA) to initiate the PIONEER Phase I/II study of GS030 in patients with Retinitis Pigmentosa (RP).
Raghavi Sudharsan, Daniel P. Beiting, Gustavo D. Aguirre, William A. Beltran
In studying the late stages of disease in two different canine models of retinitis pigmentosa, a group of progressive and inherited blinding diseases, researchers found commonalities, specifically involving the innate immune system. The findings point to potential new treatment options for the conditions.
jCyte, one of the leaders in developing cell-based therapies for RP, announces positive 12-month results from its Phase 1/2a clinical trial to treat retinitis pigmentosa with stem cells.
Thanks to everyone who rushed to our aid during our recent request for funding. I am sorry if I scared anyone. I should have stressed that the Usher Syndrome Coalition is not going anywhere! It’s really just a question of the depth of services we will be able to provide the community.
Here in the world of Usher syndrome, we are torn asunder by the forces of the future. Everyone looks ahead to a time when there will be treatments, when there will be a cure, when things are fixed.
Usher syndrome is the most common cause of deafness associated with visual loss of a genetic origin. The purpose of this paper is to report very severe phenotypic features of type 1B Usher syndrome in a Saudi family affected by a positive homozygous splice site mutation in MYO7A gene. This mutation manifested with advanced retinal degeneration at a young age.
What this means for Usher syndrome: Individuals with this particular mutation may experience more severe symptoms than other Usher 1B patients.
Geng R, Omar A., Gopal SR, Chen DH, Stepanyan R, Basch ML, Dinculescu A, Furness DN, Saperstein D, Hauswirth W, Lustig LR, Alagramam KN
Researchers developed a new USH3 mouse model that displays delayed-onset progressive hearing loss, then tested a viral therapy to preserve hearing in the mouse models. Their results show that gene therapy is a promising approach to preserve hearing in USH3 patients.
While we wait for treatments, the Coalition is what makes life bearable.
Samantha R. De Silva, Alun R. Barnard, Steven Hughes, Shu K. E. Tam, Chris Martin, Mandeep S. Singh, Alona O. Barnea-Cramer, Michelle E. McClements, Matthew J. During, Stuart N. Peirson, Mark W. Hankins and Robert E. MacLaren
Oxford researchers have shown that gene therapy might help reverse blindness caused by retinitis pigmentosa by reprogramming cells at the back of the eye to become light sensitive.
View the journal publication of this study: http://www.pnas.org/content/early/2017/09/26/1701589114
If you believe the Usher Syndrome Coalition has improved your life in any way, I hope you will join me in ensuring its continued existence.
In this USH Talk, Hester van Diepen provides an overview of the Usher development program at ProQR Therapeutics as an approach for possible future treatment of USH2A-associated retinitis pigmentosa.
Alice Emptoz, Vincent Michel, Andrea Lelli, Omar Akil, Jacques Boutet de Monvel, Ghizlene Lahlou, Anaïs Meyer, Typhaine Dupont, Sylvie Nouaille, Elody Ey, Filipa Franca de Barros, Mathieu Beraneck, Didier Dulon, Jean-Pierre Hardelin, Lawrence Lustig, Paul Avan, Christine Petit, Saaid Safieddine
Scientists have recently restored hearing and balance in a mouse model of Usher syndrome type 1G characterized by profound congenital deafness and vestibular disorders caused by severe dysmorphogenesis of the mechanoelectrical transduction apparatus of the inner ear's sensory cells. These findings open up new possibilities for the development of gene therapy treatments for hereditary forms of deafness.
Katharine Rose blogs about how the essence of life seems to always come down to the small and simple things, to the things we often don’t think about, the things we take for granted, the things we forget are gifted to us as human beings: our ability to see and hear, taste and smell, walk and breathe.
I'm grateful to have had so many decades of my life completely unaware of Usher syndrome. But now that I know that I have it, I think often about how Usher syndrome isn't something that everyone knows about.
The primary purpose of the Own the Equinox campaign is to raise awareness about Usher syndrome. The second purpose of Own the Equinox is to raise funds for the Usher Syndrome Coalition.
Usher Syndrome Awareness Day and the Own the Equinox campaign are first about raising awareness for Usher syndrome. By building a community and gaining global recognition for Usher syndrome we move closer to a cure.
A plea to the Usher syndrome community: do not rely on testimonials and press releases to influence your medical treatment decisions.
Approved by the U.S. Food and Drug Administration in June, Cochlear’s Nucleus 7 Sound Processor can now stream sound directly from a compatible iPhone, iPad or iPod touch to the sound processor.
Nikolas L. Jorstad, Matthew S. Wilken, William N. Grimes, Stefanie G. Wohl, Leah S. VandenBosch, Takeshi Yoshimatsu, Rachel O. Wong, Fred Rieke, & Thomas A. Reh
NEI-funded researchers use a clue from zebrafish to discover the cues that reprogram Müller glia into retinal neurons.
In this USH Talk, Dr. Shannon Boye summarizes efforts to develop a dual AAV vector-based gene therapy for Myosin7a Usher syndrome (USH1B). The drawbacks of USH1B mouse models and a rationale for testing these vectors in a more clinically relevant species are discussed.
Sarath Vijayakumar Frederic F. Depreux Francine M. Jodelka Jennifer J. Lentz Frank Rigo Timothy A. Jones Michelle L. Hastings.
These findings provide the first direct evidence of an effective treatment of peripheral vestibular function in a mouse model of USH1C and reveal the potential for using antisense technology to treat vestibular dysfunction.
If you’ve followed any of my involvement with the Usher community over the years, from blog posts to ARVO updates to speaking at our family conferences and making dorky USH Talk videos, it should come as no surprise to you that I’m a big proponent of science communication and outreach.
In this USH Talk, Dr. Hannie Kremer explains genetic testing of the USH2A gene, as conducted at the Radboud University Medical Center in Nijmegen, Netherlands.
Scientists at the Boston Children’s Hospital, Massachusetts Eye and Ear and Harvard Medical School have spent several years refining a technique to repair one of the common genetic disorders that cause deafness, offering hope to millions. The genetic disorder they repaired is Usher syndrome.
Jennifer Phillips, Ph.D. highlights the importance of forging "connections with people who have expertise in different areas" of Usher syndrome.
Jennifer Phillips, Ph.D." on defining “Failure”: Disclosing when things don’t work and understanding WHY is a really important, though often overlooked realm of research. Here are a couple of USH1 research stories from today’s presentations that illustrate that point.
Jennifer Phillips, Ph.D.: Several of the talks on Day 3 at ARVO 2017 delved into the biology of what, specifically, causes photoreceptor cells to die in retinitis pigmentosa patients.
Jennifer Phillips, Ph.D. recaps ARVO 2017 Day 2 with highlights on Usher syndrome type 2A research from Erwin van Wijk and colleagues at Radboud University Medical Center in the Netherlands and RP research by Neena Haider and her team at Massachusetts Eye and Ear.
Jennifer Phillips, Ph.D. shares highlights of Usher syndrome research from ARVO 2017.
If you tell your story, if you share your dream, if you reach out for help, you might just be surprised who will reach back out to help and tell their story, and share their dream, to you.
Encouraging signs this week that the FDA is serious when it granted Regenerative Medicine Advanced Therapy (RMAT) status to the CIRM-funded jCyte clinical trial for a rare form of blindness. This is a big deal because RMAT seeks to accelerate approval for stem cell therapies that demonstrate they can help patients with unmet medical needs.
Dr. Gema García-García shares strategies for the molecular diagnosis of Usher syndrome used at the Health Research Institute Hospital La Fe in Valencia, Spain. | En este USH Talk, Dr. Gema García-García presenta strategias para el estudio molecular del Síndrome de Usher.
jCyte is working on a treatment for the broad spectrum of Retinitis Pigmentosa.
Jie Zhu, Chang Ming, Xin Fu, Yaou Duan, Duc Anh Hoang, Jeffrey Rutgard, Runze Zhang, Wenqiu Wang, Rui Hou, Daniel Zhang, Edward Zhang, Charlotte Zhang, Xiaoke Hao, Wenjun Xiong, Kang Zhang.
Using the gene-editing tool CRISPR/Cas9, researchers have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.
For more information on this study: https://www.nature.com/cr/journal/vaop/ncurrent/full/cr201757a.html
In this USH Talk, Megan Cote provides a brief overview of the National Center on Deaf-Blindness (NCDB), their six national initiatives and ways in which they can connect families to support and training at the state and national level.
Usher syndrome is, and will remain, a rare disease. Turns out it may be rarer than we thought.
Researchers from the National Institute on Deafness and Other Communication Disorders (NIDCD) and Johns Hopkins University School of Medicine showed that gene therapy was able to restore balance and hearing in genetically modified mice that mimic Usher Syndrome.
Kevin Isgrig, Jack W. Shteamer, Inna A. Belyantseva, Meghan C. Drummond, Tracy S. Fitzgerald, Sarath Vijayakumar, Sherri M. Jones, Andrew J. Griffith, Thomas B. Friedman, Lisa L. Cunningham, Wade W. Chien
For more information on this study: http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(17)30013-8
Splash Magazines' Andrew DeCanniere interviews Mark Dunning, Chair of the Coalition, about the upcoming USH Connections Conference, the state of Usher syndrome research and the Usher Syndrome Coalition community.
Foundation Fighting Blindness Press Release (Columbia, MD) - A Cautionary Tale About the Need to Educate Patients and Advance Research to Produce Treatments with Proven Efficacy, Says Foundation Fighting Blindness
Harvard Stem Cell Institute (HSCI) researchers at Brigham and Women’s Hospital (BWH) and Massachusetts Eye and Ear Infirmary and colleagues from Massachusetts Institute of Technology (MIT) have developed an approach to replace damaged sound-sensing hair cells, which eventually may lead to therapies for people who live with disabling hearing loss.
Allergan and Editas Medicine have made an alliance to work with the gene-editing CRISPR to help prevent vision deterioration.
In this study, researchers introduced CRISPR into retinal cells, tested this genome tool to remove the Nrl gene in mice and three different mouse models of retinal degeneration. By measuring gene expression and examining the retinal cells, the researchers confirmed that rods became more cone-like, as predicted which allowed for rod degeneration to be prevented or slowed.
Yu W, Mookherjee S, Chaitankar V, Hiriyanna S, Kim JW, Brooks M, Ataeijiannati Y, Sun X, Dong L, Li T, Swaroop A, Wu Z
For more information on this study: http://www.nature.com/articles/ncomms14716
Scientists have developed a retinal implant that can restore lost vision in rats and are planning to trial the procedure in humans later this year. The implant made from a thin layer of conductive polymer, placed on a silk-based substrate and covered with semiconducting polymer, is being developed into a prosthetic that serves as a working replacement for a damaged retina. Based on results from initial studies, the team has concluded that the implant directly activates “residual neuronal circuitries in the degenerate retina.” Although there are no guarantees that results obtained in rats will translate to humans, the team is hopeful that they will.
What this means for Usher syndrome: This is another example of a prosthetic that could potentially replace damaged photoreceptors and potentially restore vision for those with RP.
Scientists have developed a retinal implant that can restore lost vision in rats, and are planning to trial the procedure in humans later this year. The implant, which converts light into an electrical signal that stimulates retinal neurons, could give hope to millions who experience retinal degeneration – including retinitis pigmentosa – in which photoreceptor cells in the eye begin to break down, leading to blindness.
Researchers are working to find how fish can regenerate their eyes after they have been injured and if there is a way to make this happen the same way in a human eye.
Mark Dunning does the Usher Dance Challenge #usher4ushersyndrome.
Kate's call for sunsets is for all of us.
In this USH Talk, Dr. Erwin van Wijk shows that AON-based splice correction could be a promising approach for the development of a future treatment for USH2A-associated retinitis pigmentosa caused by the deep-intronic c.7595-2144A>G mutation.
Scientists from Brigham and Women’s Hospital (BWH), MIT, and Massachusetts Eye and Ear believe they may have found a way to treat hearing loss by regenerating hair cells in the inner ear and hope to begin clinical trials in 18 months.
The prestigious Institute of Ocular Microsurgery in Barcelona implanted the first patient in Spain with IRIS® II, a bionic vision system equipped with a bio-inspired camera and a 150-electrode epi-retinal implant that is designed to be explantable.
Not just Star Trek fiction, a new visor from eSight is a lightweight, high-contrast vision system for legally blind people.
Chimeras are incredibly useful for understanding how animals grow and develop. They might one day be used to grow life-saving organs that can be transplanted into humans.
Lukas D Landegger, Bifeng Pan, Charles Askew, Sarah J Wassmer, Sarah D Gluck, Alice Galvin, Ruth Taylor, Andrew Forge, Konstantina M Stankovic, Jeffrey R Holt & Luk H Vandenberghe.
Two back-to-back papers in Nature Biotechnology describe how a team at Boston Children's Hospital and Harvard Medical School developed a new vector for gene delivery and restored hearing and balance in a mouse model with the Ush1c mutation.
Bifeng Pan, Charles Askew, Alice Galvin, Selena Heman-Ackah, Yukako Asai, Artur A Indzhykulian, Francine M Jodelka, Michelle L Hastings, Jennifer J Lentz, Luk H Vandenberghe, Jeffrey R Holt& Gwenaëlle S Géléoc.
Working with a mouse model of a human mutation, Dr. Gwen Géléoc and colleagues delivered a normal copy of the USH1C gene to the inner ear soon after the mice were born, which led to robust improvements enabling profoundly deaf and dizzy mice to hear sounds at the level of whispers and recover proper balance function.
Dr. Gwen Géléoc shares exciting news on progress made towards gene therapy for USH1C. Working with a mouse model of a human mutation, Dr. Géléoc and colleagues delivered a normal copy of the USH1C gene to the inner ear soon after the mice were born, which led to robust improvements enabling profoundly deaf and dizzy mice to hear sounds at the level of whispers and recover proper balance function. Dr. Géléoc is cautiously optimistic that successes in the lab will someday lead to novel therapeutic approaches in the clinic.
Our latest USH Talk features researcher Dr. Jacque Duncan from the University of California, San Francisco. Dr. Duncan shares an overview of an upcoming clinical trial that aims to study the rate of progression of USH2A related retinal degeneration: The RUSH2A Study.
Children with Usher syndrome will be the major beneficiaries of research on Usher syndrome. But where are these children? Nancy O'Donnell, Director of the USH Trust, ponders this question in an upcoming webinar hosted by the National Center on Deaf-Blindness.
The Foundation Fighting Blindness Clinical Research Institute (FFB-CRI) has announced an investment of up to $7.5 million to advance the potential therapy into and through a Phase II clinical trial for the usage of N-acetylcysteine-amide (NACA). NACA has recently emerged as a promising drug for Retinitis Pigmentosa because in several FFB-funded lab studies at Johns Hopkins University, it has slowed down retinal degeneration.
Watch our latest USH Talk from Boston Children's Hospital pediatric ear, nose and throat doctor, Margaret Kenna.
Family physician, Annmaree Yee, shares what it was like coming out of the closet with Usher syndrome.
Watch our latest USH Talk from Certified Genetic Counselor and Coalition Board Director, Karmen Trzupek: Genetics 101
So here we are, a group of diverse people, angry, frustrated, worried, and shocked. Yet, despite all of that, we here in the Usher Syndrome Community have NEVER been more united.
This Giving Tuesday, we're giving back to YOU, our USH Family, with the release of our first USH Talk, a new podcast for the Usher syndrome community.
Researchers have discovered a holy grail of gene editing -- the ability to, for the first time, insert DNA at a target location into the non-dividing cells that make up the majority of adult organs and tissues. The technique, which the team showed was able to partially restore visual responses in blind rodents, will open new avenues for basic research and a variety of treatments, such as for retinal, heart and neurological diseases.
Mark Dunning describes how the one thing he did right as a parent is all the stuff he did wrong. He failed. Often miserably.
Usher syndrome has brought Kate to a crossroad, but she is determined to choose the right path.
Good news! There are a LOT of potential treatments coming for people with Usher syndrome.
Frederic F. Depreux, Lingyan Wang, Han Jiang, Francine M. Jodelka, Robert F. Rosencrans, Frank Rigo, Jennifer J. Lentz, John V. Brigande and Michelle L. Hastings.
ASO delivery to the intra-amniotic cavity modulates neonatal gene expression and may serve as a therapeutic intervention in itself or when paired with a suitable postnatal therapeutic strategy. Further optimization of the method will broaden the potential impact and applicability of this approach.
This battle with Usher syndrome is never going to be over. Not until we truly have won.
One day Usher syndrome will be no more, our efforts possibly celebrated but then, eventually, forgotten.
Danay's passion in life is to spread awareness of Usher syndrome and advocate for the deafblind community.
It became very clear to Molly at 14 years old that she somehow needed to raise awareness of her condition to educate and inform those around her about how she felt, what she needed and how they could help.
Qing Fu, Mingchu Xu, Xue Chen, Xunlun Sheng, Zhisheng Yuan, Yani Liu, Huajin Li, Zixi Sun, Huiping Li, Lizhu Yang, Keqing Wang, Fangxia Zhang ,Yumei Li, Chen Zhao, Ruifang Sui, Rui Chen.
This study aimed to identify the novel disease-causing gene of a distinct subtype of Usher syndrome.
UsherKids Australia was born from hope and the desire to make the journey through diagnosis and treatment easier for the Usher syndrome families that will follow in our path.
Here we are, celebrating the second annual “Own the Equinox” campaign for Usher Syndrome Awareness Day. Carol Brill hopes we do not have too many more of these campaigns.
Zong, Chen, Wu, Liu, Jiang.
Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.
We are all working together to eradicate Usher syndrome from the face of this earth, and we will win.
Sophia's thoughts on Usher syndrome: "We need to raise awareness, stand united, educate and find some damn cures. I believe through the Own the Equinox campaign we can do that."
We could change things because now we were two: two families in one region with all the same doctors. We had the power of our voice to advocate for all families with kids with Usher syndrome in Australia. And so UsherKids Australia was born.
Life is full of challenges. This is Sarah's. And as we approach Usher Syndrome Awareness Day, reading the stories, learning more, and helping us inspire change is yours.
Diana is owning the equinox in Mexico. "A new journey is just starting, for our challenge and for our cause. There are new opportunities to witness kindness, to learn something, to change our possibilities, to prove ourselves again that we can do more than we believe."
Bettina likes to use the words fighters, surfers and brave to describe children with Usher syndrome. She uses the same words to describe their families. Here's why...
Caroline Brown, Fairbanks Alaska resident and marathoner, passes the marathoning baton to her 6 year old boys for the second Own the Equinox campaign. Galen (with USH 1b) and David will run their own fundraiser with hopes of crushing their mom's performance last year!
How many people have we met and how many stories have we shared, and how many times have we cried together, and laughed together and been able to bond with those in our Usher Family whom we never would have met before?
Mary O'Brien was not a doctor. She wasn’t a professional in the field. She didn’t even have a family member with Usher syndrome. But she had a knack for treating Bella, for helping her deal with Usher syndrome.
As with Chloe's experience of parenthood in general, life post-Usher diagnosis has consisted of a series of phases.
In honor of Usher Syndrome Awareness Day on September 17th, Bill Barkeley, deaf-blind adventurer, advocate & storyteller, is hiking the Camino de Santiago - 533 miles from France into Spain.
Ryan Thomason is a husband, father, runner and a nerd with Usher syndrome Type 2. He describes how his life has changed over the past year because of Usher syndrome.
Nancy Corderman and Kidz b Kidz are giving a face and a voice to Usher syndrome so we can raise awareness and funds.
Clare Weigel describes how on March 22, 2013 everything transformed about her, the way she thought, the way she saw the world, and her perception of herself.
Today Martha along with her guide dog, Alvin, begin a walking and literary journey over the next 26 days for the Usher Syndrome Coalition’s “Own the Equinox” campaign.
Last year, throughout the first Own the Equinox campaign, Kate was on the outside looking in. Now, this year, she is ready to step out and speak up.
We live with Usher syndrome, and I mean live with it. Every day it is there, always there.
Walking or running isn’t your thing? Well, that’s OK. There are lots of ways you can raise awareness about Usher syndrome.
Break out the canes, harness up the dogs, grab an elbow and give a face to Usher syndrome.
Booked my flight to Australia. On Usher Syndrome Awareness day I will be Owning the Equinox with Usher families in Melbourne.
Last year we said we needed an Usher Syndrome Awareness Day. Then we went out, and with the help of Senator Wyden and his staff, we got one. The third Saturday in September was declared “Usher Syndrome Awareness Day” and written into the Congressional Record.
Poetry and prose by Kate Morell reflecting on the role Usher syndrome has played in her life.
Our apologies to anyone who wished to attend the 2016 Usher Syndrome Family Conference in Seattle but has not yet registered.
The Usher Syndrome Coalition was one of the grant recipients selected from a pool of 137 applicants requesting over $1.4 million in total. Global Genes is committed to meeting the collective need of the 350 million patients and hundreds of advocacy groups fighting for treatments and cures for over 7,000 rare diseases.
Moira Shea, the Vice Chair of the Usher Syndrome Coalition, writes about how she came to her "a-ha" moment while living with Usher syndrome.
‘I wish I were a psychologist,’ I think. ‘I wish I knew exactly what to say.’ Sometimes I shy away from writing, not knowing exactly what to say. Afraid my words may not be exactly what others want to read.
Kumar N Alagramam, Suhasini R Gopal, Ruishuang Geng, Daniel H-C Chen, Ina Nemet, Richard Lee, Guilian Tian, Masaru Miyagi, Karine F Malagu, Christopher J Lock, William R K Esmieu, Andrew P Owens, Nicola A Lindsay, Krista Ouwehand, Faywell Albertus, David F Fischer, Roland W Bürli, Angus M MacLeod, William E Harte, Krzysztof Palczewski & Yoshikazu Imanishi.
A new study published in Nature Chemical Biology reports the first small molecule targeted therapy for progressive hearing loss in a mouse model of USH3, an USH classified by progressive loss of hearing and vision starting in the first few decades of life along with variable balance disorder.
The key to advancing research into treatments for Usher syndrome is community. Not just a community, but a genetically-diagnosed and accessible community.
The Usher Syndrome Coalition spent a busy two days in Washington, DC. For those of you in the US, stay tuned for a call to action very soon.
To be fiercely independent. Determined. Persevering. Tenacious. Kate wonders if these qualities go hand in hand with Usher syndrome.
Mark Dunning describes his dream of the Usher Syndrome Coalition working with researchers and the National Institutes of Health to identify the most valuable research and the steps that will quickly deliver viable treatments to the Usher syndrome community.
Researchers study genotype–phenotype correlations and compared visual prognosis in Usher syndrome type IIa and nonsyndromic RP.
In the next month, scientists from RetroSense Therapeutics will inject a virus deep into the retina of legally blind human volunteers. If this works, it means that optogenetics — a revolutionary neuroscience technique using channelrhodopsin-2 and other light-activated proteins — is feasible in humans as therapy.
If only I had left my words to be found. If only I had the voice to speak the words I wrote. All I had to do was tell someone, anyone. All I had to do was tell someone those words.
Astra Dinculescu, Rachel M. Stupay , Wen-Tao Deng, Frank M. Dyka, Seok-Hong Min, Sanford L. Boye, Vince A. Chiodo, Carolina E. Abrahan, Ping Zhu, Qiuhong Li, Enrica Strettoi, Elena Novelli, Kerstin Nagel-Wolfrum, Uwe Wolfrum, W. Clay Smith, William W. Hauswirth.
The ongoing challenge to develop an animal model mimicking the effects of Usher III (in particular, the loss of vision) makes it impossible for researchers to test therapies in development using conventional means. This study has important implications for designing gene therapy studies in a rational manner, to produce Clarin-1 in the correct cell type and at levels that mimic its natural production.
Usher syndrome can mean a lot of things, including community and friendships and family. Wonderful uplifting exhilarating things. But Usher syndrome is also a place with bogs and lowlands where the mist gathers and the sadness pools.
Hidekane Yoshimura, Maiko Miyagawa, Kozo Kumakawa, Shin-ya Nishio, and Shin-ichi Usami.
This first report describing the frequency (1.3–2.2%) of USH1 among non-syndromic deaf children highlights the importance of comprehensive genetic testing for early disease diagnosis.
Born in Italy, Dario Sorgato was diagnosed with Usher syndrome type II at the age of 16. Dario describes his passion for travel and adventure and some tips he has collected along the way.
Experiences of a Young Clueless Boy: A little brother's view of Usher syndrome.
Meet Nancy O'Donnell, the new Director of the Usher Syndrome Coalition's International Registry. Nancy looks forward to meeting YOU, the experts with Usher syndrome around the world.
A research group in Valencia, Spain is investigating new therapeutic approaches for Usher syndrome, including the potential impact of vitamins and antioxidants to reduce the progression of the disease.
Moira Shea has Usher syndrome 2A, wears hearing aids and is totally blind. She also has a rock star guide dog named Finnegan.
Licensed genetic counselors Andrea Oza and Danielle Azzariti provide a glimpse of the inner workings of a genetics laboratory and the value of sharing information within the research community.
Maha S. Zaki, Raoul Heller, Michaela Thoenes, Gudrun Nürnberg, Gabi Stern-Schneider, Peter Nürnberg, Srikanth Karnati, Daniel Swan, Ekram Fateen, Kerstin Nagel-Wolfrum, Mostafa I. Mostafa, Holger Thiele, Uwe Wolfrum, Eveline Baumgart-Vogt, Hanno J. Bolz.
This paper found that a family with severe enamel dysplasia that was initially diagnosed with Usher syndrome didn’t have Usher syndrome but instead had mutations in the PEX6 gene.
In the first of our Guest Research Blog Series, we hear from Dr. Gwenaëlle Géléoc who is working to restore hearing in a mouse model of Usher syndrome that would otherwise be deaf. "My hope is that successes in the lab will one day be translated into treatments for Usher patients."
Your participation in the Usher syndrome community is vital to us. The registry is a powerful tool for learning about Usher syndrome and could possibly be the first step to finding new treatments. All of that starts with you.
The Usher Syndrome Coalition provides critical support for research. The Usher Syndrome Coalition does not fund research or do research. But we provide everything else, literally everything else, that is necessary to bring treatments to the clinic.
Daily Mail UK story on sisters India and Samira Cox and how Usher Syndrome has impacted their lives.
Here in the U.S. we are coming up on our traditional Thanksgiving Holiday. I figured it was a good time to say thank you to everyone who has helped the Usher Syndrome Coalition and the Usher syndrome community this year.
The Usher syndrome community lost one of our best this week when Steffen Suchert passed away.
Bella is fine. Julia and I are both under strict orders to stop worrying. She doesn’t like seeing us sad or mopey. She doesn’t want us to ask how she is doing. The answer is she is fine.
There is a formula for finding treatments for Usher syndrome and getting them into the clinic. Mark knows because he just made it up.
Kerry Thompson shares her story about the challenges she has faced living with Usher syndrome, and how her family has played an essential role in her success.
The Sun Star covers Brian Switzer and the Usher community's participation in the Equinox Marathon.
Splash Magazine interviews USH Chairman Mark Dunning.
A writer from HuffPost Impact shares her niece's story and their experience with the USH community.
Alaska Dispatch News reports on the Fairbanks’ Equinox Marathon and USH's campaign Own the Equinox.
Diana lives in Mexico City and has Usher syndrome type II. She has become an active member in the Usher community and aspires to do so much more for others with Usher syndrome, both globally and locally.
Collin helped create Ushersyndroom.nl, an organization working to raise awareness and fund treatments in Holland. Collin also has Usher syndrome type 2a.
St. Louis Today writes about a special dessert served at Pastaria, which will donate a portion of the proceeds to the Usher Syndrome Coalition.
Ramona Rice has a strong desire to make a difference as a proud "Usher Chick" and feels genuinely blessed to be one of Usher Syndrome Coalition's members.
Brian Switzer has a deep love for running. He also has Usher syndrome. That won't stop him from running one of the world's most difficult marathon courses on Usher Syndrome Awareness Day.
Alaska Public Media covers Equinox Marathon runners taking part in the first ever Usher Syndrome Awareness Day and “Own the Equinox”.
Caroline Kaczor describes her unique connection to Usher syndrome and her best friend, Rebecca Alexander.
Rebecca Alexander reflects on her path towards self-acceptance. "Having Usher syndrome humbles me not just every day but often every hour and sometimes even by the minute."
On Saturday, September 19th, in honor of Usher Syndrome Awareness Day, the Rose Family will walk together in hope – because we do have much to hope for.
Dominique is working to create an Austrian Usher Community, connecting it to the worldwide Usher Family and to international experts of Usher syndrome. To her, raising awareness means giving hope to people with Usher syndrome and their families.
Lorne Marin describes how he deals with his diagnosis on a daily basis and his climb to raise awareness for Usher syndrome: “I don’t always like climbing. I always like having climbed.”
Danay shares how she has handled her diagnosis and how she endeavors to raise awareness for Usher syndrome from Brandon, Mississippi.
Markku from Finland wants to spread awareness of Usher syndrome and tell the world that a person with Usher can manage fine in life.
Anne Jalakas is a journalist at the National Resource Centre for Deafblindness in Sweden. She is helping raise awareness for Usher syndrome and the entire deafblind community.
Ryan Thomason was diagnosed with Usher syndrome when he was 27 years old. On September 19th, the world's first Usher Syndrome Awareness Day, he will run as far as he can in order to Own the Equinox.
With the autumnal equinox only two short weeks away, we need this Usher Syndrome Awareness Day. We need to Own the Equinox, push back the sunset, accomplish more than anyone thought possible.
Bettina Kastrup Pedersen works with children with Usher syndrome in Denmark. She describes these kids in three words: surfers, fighters and brave.
Lichun Jiang, Xiaofang Liang, Yumei Li, Jing Wang, Jacques Eric Zaneveld, Hui Wang, Shan Xu, Keqing Wang, Binbin Wang, Rui Chen and Ruifang Sui.
Researchers applied next generation sequencing to characterize the mutation spectrum in 67 independent Chinese families with at least one member diagnosed with USH.
Rachel Chaikof advocates for change from Cameroon for Usher Syndrome Awareness Day.
In the build up to Usher Syndrome Awareness Day, Chloe is tweeting excerpts from a love letter that she is writing to her daughter, about the hopes and dreams she has for her in spite, because and in the face of Usher syndrome.
Carol Brill refuses to remain invisible as she passionately raises awareness for Usher syndrome and campaigns the Irish government to recognise deafblindness as a unique disability.
Moira Shea can see the treatments coming. They are just ahead of us. Usher syndrome will fade away as our vision for a cure remains strong. So set the challenge for September 19th and own the equinox, when the world goes more into darkness than light. The light will come back.
Since Day 1, Elise and her family have been trying to make Usher syndrome common knowledge.
In honor of Usher Syndrome Awareness Day on 19 September, Molly wants to show the world what our community looks like.
Every day, a person with Usher syndrome faces numerous obstacles. Despite this, Jessica refuses to let anything stop her.
Dave is the father of two children, the youngest has Usher syndrome. The family live in Melbourne, Australia, where Dave will run a marathon on 19 September for Usher Syndrome Awareness Day.
Caroline Brown, Fairbanks resident, marathoner, and most importantly, mom to Galen (5) who has Usher syndrome—provides an initial glimpse into her world of running the Equinox marathon as a fundraiser for Usher syndrome research.
Zhai, Jin, Gong, Qu, Zhao, Li
Ophthalmic examinations and audiometric tests were performed to identify the pathogenic mutations in a Chinese pedigree affected with Usher syndrome type II (USH2), which revealed distinguished clinical phenotypes associated with MYO7A and expanded the spectrum of clinical phenotypes of the MYO7A mutations.
It’s time for our grassroots efforts to go global. Let’s make our Usher Syndrome Awareness Day span the world. You can help in ways big and small. We have a size that fits you and whatever you give will help.
Maybe running isn’t your thing. Or maybe you have an idea of your own. Go for it! Create your own a-thon and help us Own the Equinox.
You want people to know about Usher syndrome, to understand it, to fund it, to cure it. But, boy, that mile a day seems like a lot of effort. You really just don’t feel like getting off the couch.
Article detailing Lizzy Myers and her parents and their efforts to take advantage of her sight in the face of her Usher Syndrome diagnosis.
Finding treatments for the most common cause of combined deafness and blindness is extremely difficult. It seems insurmountable. But is it?
Did you know that regular exercise may actually help you keep your vision longer?
We need to cure the most common cause of combined deafness and blindness. And we can do it. On September 19th, Usher Syndrome Awareness Day, let’s demonstrate that power to make the impossible possible.
Article describing the Myers family and their daughter Lizzy living with her diagnosis of Usher Syndrome.
"Staying Alive: Saving the Retina through Neuroprotection" by Ben Shaberman, Director, Science Communications, presented at the USH2015 Family Conference
On September 19th, we want to Own the Equinox. We need a global Usher Syndrome Awareness Day and we're going to have one.
In addition to the unprecedented ability to target and study disease genes, CRISPR/Cas has promising potential for disease therapy as well. There is reason to hope that this strange bacterial innovation could someday provide a cure for human diseases like Usher syndrome.
We no longer have to hope that someday there will be treatments. There will be. So it’s time to dream bigger than just treatments. It’s time to dream about treatments that come in time...
I have no qualms about sharing my deepest fears with people in this Usher syndrome community. But I don’t really like writing about myself. And I really don’t like asking for help. Today I am going to attempt to do both. Hopefully you will understand why.
Massachusetts researchers have made a significant advancement toward a gene therapy treatment that would reverse deafness.
I am home.
The suitcase is unpacked.
And I am home.
The following speech was delivered by Mark Dunning at the dedication ceremony for the William J. Kimberling Usher Research Laboratory.
We are in the process of transitioning to a new website. The new platform will be more accessible and available in more languages. It will also undoubtedly come with some bugs so please bear with us during the transition. Oh, and shout out a big thank you to all the volunteers, high school and college interns, who have done most of the leg work setting up the site.
Science is trial and error. Only 1 in 12 potential treatments which are tested in humans actually make it to clinic. But that number is misleading. Those that don’t result in a clinical treatment aren’t necessarily failures. They are practice runs used to adjust dosage, delivery method, and measurement criteria. We learn something from every clinical trial, but we often need a lot of them to get a treatment to clinic.
Up to this point, the focus of the presentations I’ve attended here has been on interventions designed either to correct RP at the molecular or cellular level. The progress, while promising, is also slow and complex. We’re not there yet, and the question remains for people who have RP now, what can we do in the meantime?
Part of the challenge in working out treatments for RP is that the clock is always ticking. While researchers and clinicians work like mad to figure out the mechanisms of different genetic disorders, our patients are steadily losing retinal cells.
Day 2 is in the books, and, whether by virtue of my coincidental itinerary selection or of the magnificent foresight of the ARVO Annual Meeting organizers, today’s talks and posters were the ideal ‘next level’ to the material that was presented on Day 1.
Greetings from Denver, and apologies for the long silence on this blog from me. If you were wondering whether I’d lost interest in Usher syndrome, quite the contrary! I’ve been neck-deep in some very exciting research over the past year, some of which I’ll be presenting here this week.
Bill Kimberling is a man with stories. Hundreds of stories. Thousands of stories. All of them your stories. He compiled them over decades of working with Usher syndrome families. The data, the bland details, are cataloged in wrinkled medical records stuffed in thick manila folders. The good stuff, the touching, the compelling, the inspiring, well, that he keeps locked safely in his heart.
In honor of the dedication of the William J. Kimberling Usher Research Laboratory at the University of Iowa, I ask you, I implore you, to take a few moments and share your stories of Bill.
You’re probably familiar with the old expression that “nothing is free, and there’s always a catch.” Fortunately, there are a few shining exceptions to this rule, and the National Deaf-Blind Equipment Distribution Program, also known as iCanConnect, is one of them.
I had the honor of attending Deafblind Awareness Day at the Massachusetts State House recently. I have attended many of these days and they are always amazing. I would describe why I enjoy them so, but Carl Richardson, the State House ADA Coordinator, gives a much more eloquent description than I ever could: Humbled and awed.
Researchers investigated the proportion of exon deletions and duplications in PCDH15 and USH2A in 20 USH1 and 30 USH2 patients from Denmark.
A few years ago there was a 5.8 earthquake in Virginia that literally shook Washington, DC. For people with Usher syndrome, there has now been a similar ground shift in Washington. Yesterday, March 19th, 2015, we held a Congressional briefing on Usher syndrome. It was an incredibly busy and exciting day.
USA Today will be shining a spotlight on Usher Syndrome in MediaPlanet's Vision and Hearing Health supplement.
The Usher III Initiative's Scientific Director, Dr. David Saperstein, shares the latest updates on treatments under development for Usher syndrome type 3.
This blog has always been about families. Sure we talk about the science of Usher syndrome, the politics of Usher syndrome, the funding of Usher syndrome, but all of it, in the end, comes back to the impact of Usher syndrome on families.
Family has always been the way through this. Family is the treatment. Family is the cure. That’s how we survive Usher syndrome. We rely on family for support, for assistance, for a shoulder to cry on when things get hard.
On March 19th we will host a Congressional briefing on Usher syndrome. Edwin Stone, MD, PhD, from the Stephen A. Wynn Institute for Vision Research at the University of Iowa will be the featured speaker. Ed will be talking about the exciting state of Usher syndrome research and the need
A reflection on life according to Megan Kennedy, who was diagnosed with Usher Syndrome at 22.
There are several phases of a clinical trial but phase I is the hardest. It’s that terrifying and exhilarating moment when a potential treatment that has only been tried in animals is tried in a human being for the first time.
Let’s laugh for a little while. I want to laugh. I have clinical depression and laughing is hard. It feels like gargling glass. I used to have a great sense of humor. I want it back.
I have a confession. I hate asking for money. Despise it. The fact that I am doing so should tell you just how important I believe the Usher Syndrome Coalition is to finding treatments for Usher syndrome. I have estimated that we will need $50 million annually for each of the next 18 years if we are going to find treatments for every person of every age with every type of Usher syndrome everywhere.
I am 16 years old and have Usher syndrome. I love horseback riding, photography, and agility with my dogs. This week, I am going to Ireland with my dad. I would not be able to go on this trip if it weren't for Usher Syndrome. I am very excited to meet new people and explore Ireland.
It is Halloween week so it is a good time to write about something very scary. We are at a critical point in the search for Usher treatments. There are a number of promising developments in the lab that could lead to treatments. These are getting close to clinical trial but they may never reach the clinic for one very avoidable reason:
Sweden's Nationellt Kunskapscenter För Dövblindfrågor writes about Usher Syndrome and the coalition's achievements and goals.
The Usher Syndrome Coalition's mission is to raise awareness and accelerate research for the most common cause of combined deafness and blindness. The Coalition also provides information and support to individuals and families affected by Usher syndrome.
While my dad and others speak, I’m taking over the Usher Syndrome Coalition’s Twitter handle, @UsherCoalition. To help raise awareness for Usher syndrome, I’ll be live tweeting the event with the hashtag #USHFAMILY.
Fifty million dollars is a big number, an intimidating number, a number beyond the imagination of most of us. Personally I think in hundreds and thousands. Anything larger than my mortgage is almost beyond comprehension to me. Oh, I dream of winning the lottery and I can imagine owning an island in the South Pacific. But that is fantasy. It’s not something that I can really see happening. No, fifty million dollars is forever going to be beyond my reach.
Whew. It’s been a tough year in the Dunning household. I’m not writing this to appeal for sympathy but rather out of exasperation. And, as always, it’s all about Usher syndrome even when it is not. In this case, it’s about Bella and her belly.
I have not read Rebecca Alexander’s new book Not Fade Away: A Memoir of Senses Lost and Found. Don’t get me wrong. I want to read it. I was even sent an advance copy by the publisher, which was very thoughtful. Problem is I haven’t seen the book since.
Mike Walsh reminisces on his experience speaking on the Family Panel at the 2014 Usher Syndrome Family Conference at Harvard Medical School.
There is dog named Tater. And there is Bella.
Usher syndrome is about uncertainty. It is not knowing. It is fearing the future and desperately clinging to joyful moments in the present.
In an inspired moment of bravado, someone you know decided to go undercover and pretend to be blind, white cane and all, at Boston’s annual July 4th celebration, moved to July 3rd due to Hurricane Arthur.
I was lucky to meet Mark, Julia, Bella and Jack Dunning a few years ago in Boston as a result of my mum finding the Usher Syndrome Coalition online.
Though he desperately wanted to be there, Bill Kimberling could not attend the International Symposium on Usher Syndrome. Personally, I couldn’t get through one presentation without thinking about Bill. Seems like I wasn’t alone as his name and likeness were on a lot of presentations.
It’s over. The largest gathering of the Usher syndrome community in history. Three days, four nights, nearly fifty speakers, dozens of interpreters, and more than three hundred attendees. The International Symposium on Usher Syndrome, #USH2014, is now history.
Rajarshi Ghosh, Wang Likun, Eric S. Wang, B. Gayani K. Perera, Aeid Igbaria, Shuhei Morita, Kris Prado, Maike Thamsen, Deborah Caswell, Hector Macias, Kurt F. Weiberth, Micah J. Gliedt, Marcel V. Alavi, Sanjay B. Hari, Arinjay K. Mitra, Barun Bhhatarai, Stephan C. Schürer, Erik L. Snapp, Douglas B. Gould, Michael S. German, Bradley J. Backes, Dustin J. Maly, Scott A. Oakes, and Feroz R. Papa.
Allosteric inhibition of the IRE1α RNase preserves cell viability and function during endoplasmic reticulum stress.
New research shows that modifying a particular protein, IRE1, can put off cell death.
I was first diagnosed with deafness as an infant and was one of the first 200 children in the U.S. to receive a cochlear implant as part of a clinical trial. How did I get on that short list? My parents stayed on top of the latest research and reached out to numerous professionals. Years later, at the age of 19, I would come to find out that I had a new battle to overcome.
When Bella was born she was bald as a cue ball. It took almost a year before she had any hair. I couldn’t imagine her with hair. That first year we went to a support group for parents (for deafness, not baldness).
Katherine Lafferty is a certified and licensed genetic counselor in Massachusetts. She is currently a genetic counselor at the Laboratory for Molecular Medicine at Partners HealthCare Personalized Medicine in Cambridge, MA where she and her colleagues work at the forefront of clinical genetic testing in the areas of hearing loss and Usher syndrome. Katherine also provides genetic counseling to patients and families in the Department of Otolaryngology at Boston Children’s Hospital.
I thought I would write one last time about mental illness and Usher syndrome. Then I’m done. It’s getting too depressing, pun intended (see, my sense of humor IS coming back!). One thing I’ve always struggled with is the difference between depression and anxiety. I tried to write about it a while back but I failed miserably. Now that I’ve been through this experience, I think I can both differentiate between the two and describe their impact a little bit better.
My wife Julia and I learned that our daughter Bella had hearing loss when she was an infant. She was identified through a pilot program for newborn hearing screening. We learned sign language. We tried hearing aids. When she was two, she got her first cochlear implant. There were a million otolaryngology visits. She had hours of speech therapy. We attended hearing loss support groups for parents. Our lives revolved around hearing loss.
From July 10-12th the Harvard Medical School’s Joseph B. Martin Conference will open its doors for the 2014 International Symposium on Usher Syndrome and Family Conference. This means that the world’s leading Usher syndrome experts and researchers will meet face-to-face with the families they work tirelessly to treat.
I don’t know who you are but I know if you are reading this blog post, you should attend the symposium. You should attend because you are a member of the Usher syndrome community and this will be the largest gathering of the Usher syndrome community in history.
Gene therapy is still a relatively new development, and so far, the only USH target being delivered via viral vector in clinical trials is MYO7A (USH1B). There are a few different reasons for this, but all boil down to a numbers game.
Preventing or slowing the rate of retinal cell degeneration in the various forms of RP has been a well-covered topic at the past few ARVO meetings, and this year is no exception.
Since I've spent the past few days talking in generalities, I’ll spend today’s blog giving a brief overview on the research specifically dealing with Usher syndrome.
Another day of scientific discovery has come and gone here at ARVO. Continuing with yesterday’s inspirations from Chris Anderson’s book “Makers”, the theme of today was Crowdsourcing.
Hello once again from ARVO! I’m writing to you from the Orange County Convention Center in Orlando, having just completed the first day of the 2014 Annual Meeting.
About a month ago I wrote that I was dealing with depression and anxiety. I wrote at the time that I would share my experiences in the hope that it inspires others to seek help. Well, we’re one month in and a lot has happened. It seemed like the right time to answer the question a good friend asked me:
My name is Mark Dunning from the state of Massachusetts. As Chairman of the Coalition for Usher Syndrome Research, I am here on behalf of the Usher syndrome community to respectfully request this committee encourage NIH to prioritize research that will eventually expand treatment options for individuals suffering from the severe hearing and vision loss related to Usher syndrome.
I don’t live with Usher syndrome. Not really. My husband does, so I’m a bit like a not-so-silent bystander watching and participating in his journey.
My son asked me last night what happened to me. He was crying his way to sleep. Again. He says he does so every night because he is worried about me. “You never laugh anymore,” he said, “I don’t understand. I just want things back to the way they were.”
Bella wants to drive. I knew this was coming. I’ve seen it on the horizon for the last eight years. I’ve put off addressing it as long as possible in hopes that some epiphany would strike me on how to handle the situation. It hasn’t happened. Bella turns sixteen in October and Bella wants to drive.
A poem by Mani G. Iyer
This post is about you. It’s a thank you. Your efforts are starting to have an impact on the federal funding levels for Usher syndrome. Now you may be thinking ‘he doesn’t mean me. I didn’t do anything.’ But simply by reading this blog, you have done something to help.
I have two children. If you read this blog frequently, you know about my daughter Bella. She has Usher syndrome and I write about her a lot. I also have a son named Jack who is now 12 years old. He does not have Usher syndrome and so I don’t write about him very often. He tends to be a supporting character in the stories.
We have big news on our efforts to raise the profile of Usher syndrome in Washington, D.C. The following language is included in the omnibus spending package that was sent to the President for his signature today:
I know that at least some of you read the post I authored last August on a newly published report on acupuncture treatment for retinitis pigmentosa. Since that time, there has been quite a bit of continued discussion in the Usher community surrounding the October publication of the study in the journal Clinical and Experimental Optometry, at which time the protocol was made available for other acupuncturists to purchase. Given this ongoing discussion, which has taken place alongside a marketing campaign for the practice where this procedure originated, it seemed like a good idea to post an update.
We Usher Coalition Bloggers are a bit of a mixed bag. Adhering to the age-old advice for authors, we all write what we know. Mark and Kate write as people who live with the diagnosis of Usher syndrome and serve as community advocates. What I know is the science of Usher syndrome, and as such, the vast majority of my posts are heavy on facts and light on personal perspectives.
Previous cell culture studies have suggested that CLRN1, the causative gene for USH3A, is localized to the plasma membrane and interacts with the cytoskeleton. However, less is known about CLRN1’s role with vision because the mouse model does not exhibit a retinal phenotype and expression studies in murine retinas have provided conflicting results. This study described the cloning and expression analysis of the zebrafish CLRN1 gene, and report protein localization of CLRN1 in auditory and visual cells from embryonic through adult stages. The data provide a foundation for exploring the role of CLRN1 in retinal cell function and survival in a diurnal, cone-dominant species.
What this means for Usher syndrome: Zebrafish may provide a good model for studies of USH3A.
In Part I, we talked about the need for increased federal funding for Usher syndrome research. Today we’ll talk about the process for getting that funding.
Lately I have been obsessed with the question, ‘what would I miss?’
This year the Usher Syndrome Coalition went to Washington D.C. to seek increased federal funding for Usher syndrome research.
Dr Liz Ellis and Dr Liz Hodges.
This research report, funded by Sense, presents the lives of people with Usher syndrome, showing the impact of the diagnosis on their experiences; education, communication, employment, friends and family, mobility – across all areas of their lives. This report aimed to explore the questions: What do people with Usher think about having Usher syndrome? What is the effect of change on the lives of people with Usher? What do people with Usher remember of their diagnosis and what impact did it have on them?
You know Grampa didn't want to be Grampa. Grampas were old and he wasn't old. He tried out a lot of names before accepting his fate.
Foundation Fighting Blindness' deputy chief research officer, Dr. Brian Mansfield, explains how retinal researchers are working with induced pluripotent stem cells (iPSC), a patient's own skin cells, to gain a better understanding of the RP caused by defects in the gene USH2A. This basic research provides critical information for developing future treatments.
So when I read Jennifer’s take on the current clinical trials for acupuncture I wondered if maybe a focus on the clinical impact, at least in this case, was missing the point.
Sometimes being the resident scientist on this blog is a challenging job. There are promising new developments to write up, but also stories that are more complex, controversial, or just plain worrisome. I’ve put off writing this post for a while because it’s been a tough one to process, but I sincerely believe our readers need to make informed choices about any new treatment options that might come their way, and I hope this write-up will help make that possible.
Bella was twenty months old and had just come out of the surgery for her first cochlear implant. She was groggy and nauseous from the anesthetic. She had a tight wrap on her head. Tubes ran from her arms which were both wrapped to splints to keep her from fussing with her bandages. She was miserable.
Steele-Stallard, Le Quesne Stabej P, Lenassi E, Luxon LM, Claustres M, Roux AF, Webster AR, Bitner-Glindzicz M..
Screening for duplications, deletions and a common intronic mutation detects 35% of second mutations in patients with USH2A monoallelic mutations on Sanger sequencing. An overview of a study to improve the molecular diagnosis in families with USH2A by screening USH2A for duplications.
A Poem by Kate Morell
Clinical trials and studies on retinitis pigmentosa usually exclude people with Usher syndrome, at least in the early stages. The reason given is often that people with Usher syndrome not only have RP, but they also have hearing loss.
A Poem by Kate Morrell
Here we are four years later and the blog is still missing two key pieces. We need the perspective of someone living with Usher, not just an observant family member such as me. And though Jennifer and I have the United States pretty well covered (I am a proud New Englander and Jennifer is a West Coaster from Oregon), we still lack a regular international contributor. That will all change now that Kate Morrell is joining us.
ARVO 2013 concluded two weeks ago, but there are still a few more noteworthy stories from ARVO to tell, and this is one of them.
Whew! Day 4 is in the books, and what a day it was. I saw more excellent science presentations than I can count (and a few disappointing ones, too, but that’s a story for another day). I engaged in stimulating discussions about research directions throughout the day and managed to catch sight of a few Seattle landmarks while walking and talking with a colleague before hunkering down in my quaint little hotel room to write this up.
Day 3 of the ARVO meeting was filled with a lot of presentations on retinal cell biology—nitty gritty details about how tiny molecules are transported hither and yon inside the cell, and what goes wrong if the transportation system breaks down. Mother’s milk for me, but probably not for most of our readers. There were, however, a number of poster presentations that might be of general interest here:
The talks I attended today were on the topics of photoreceptor cilia, Nanotechnology and Regenerative Medicine, and Stem Cell therapies. Afterward, I saw posters on a wide variety of studies related to retinal degeneration.
Greetings from sunny Fort Lauderdale Seattle, destination for this year’s ARVO meeting. I’m here all week, and I’ll be blogging on the very latest vision research going on around the world that has some relevance to Usher syndrome.
Berth Danermark, Claes Moller, Kerstin Moller, Moa Wahlqvist.
The objectives of the study reported here were to describe the physical and psychological health of persons with Usher syndrome Type II (USH2) and to explore any differences in terms of gender.
When I was 15, I was diagnosed with Usher syndrome, the leading cause of deaf-blindness in the United States. Although I’d had hearing aids since kindergarten, and could never see in dark places, it wasn’t until I started to trip over things in broad daylight that my parents became truly concerned.
We are going to Grand Cayman Island for Bella. When she was diagnosed six years ago, my wife and I decided to take her to see the world whenever the opportunity arose. It is insurance, in case the unthinkable happens and her vision fails. We want her memories filled with the world.
Researchers at the University of Wisconsin-Madison developed an innovative process to transform skin cells into retinal cells — cells that hold great promise for restoring vision.
What I’m asking is, knowing now that you have Usher syndrome, knowing how it felt to find out, would you have wanted to have known the diagnosis earlier than you did?
Testimony of Susie Trotochaud of Georgia
Just a quick post today to give you an update on another important aspect of Usher syndrome research: Funding.
A couple of new stories/updates that will probably be of interest to our readers.
Danish research by Ph.D. Jesper Dammeyer, in cooperation with educational consultant Bente Ramsing, shows that more than half of all children with Usher Syndrome develop symptoms of psychosocial dissatisfaction before the age of 18.
But we are NOT going to ignore the psychosocial impact of Usher syndrome on families. We are going to address it frequently and we are going to fight it with hope.
USA Today reports on a promising step against a genetic disease that causes deafness and gradual loss of vision -- scientists have partly restored hearing with a single injection to young mice.
Jessica Chaikof is a teenager with Usher syndrome. She wrote this poem for her high school English class and has graciously allowed us to reprint it here.
Jennifer J Lentz, Francine M Jodelka, Anthony J Hinrich, Kate E McCaffrey, Hamilton E Farris, Matthew J Spalitta, Nicolas G Bazan, Dominik M Duelli, Frank Rigo & Michelle L Hastings
New research shows that hearing and vestibular function can be rescued in a mouse model of Usher 1c using an antisense oligonucleotide.
A new study questions whether gene therapy to treat Leber congenital amaurosis type 2 (LCA2) actually saves the rods and cones, the photoreceptor cells that provide vision.
According to scientists at Washington University School of Medicine in St. Louis, "Doctors may one day treat some forms of blindness by altering the genetic program of the light-sensing cells of the eye."
Two deaf twins in Belgium recently sought, and were granted, the right to be euthanized after learning that they would soon also go blind.
I am an animal lover. I make cozy little shoebox homes for the injured birds that regularly smack into our picture windows. I carry spiders, beetles, moths and most other critters who find their way into my house outside, rather than smashing them. A happy, well-fed Golden Retriever is resting her head on my lap as I type this.
Since my return to blogging with an analysis of recent peer-reviewed literature on Usher research, another paper that will probably have relevance to a lot of our blog readers has come to my attention. In contrast to those first two papers on new Usher genes, however, this one isn’t exactly a cause for celebration.
Here is something I wrote several years ago about a vacation with the family:
Taught the kids to fish yesterday. I didn't think they'd enjoy it, but they really did. I also thought that I would. I didn't. They spent five hours fishing. I spent five hours undoing tangles and pulling lures out of trees.
When I think of candy canes, I think of two things. One, they are kind of gross. The plastic wrapping seems to be part of the candy, nearly inseparable and almost as sticky. I remember growing up that I ate as much of the wrapper as I did of the candy. To this day, when I eat a candy cane, my palate expects the taste of plastic and of my fingertips as I scrape said plastic from my tongue. And a candy cane is the only sweet that can be sucked in to weapon form. Ten minutes in your mouth produces a shiv. I can still taste the blood in my mouth from my impaled gums.
"Ray of hope for human Usher syndrome patients": Uwe Wolfrum and his colleagues at Johannes Gutenberg University Mainz are increasing our understanding of Usher syndrome.
Oh, the hormonal tempest that is a teenager. My daughter can argue about the color of the grass. She can break down crying over who was handed the dinner rolls first because, clearly, it was a statement on who among the children was more loved. I’m afraid to make eye contact with my daughter, so it’s hard to imagine the stress of discussing something difficult, like a new diagnosis of Usher syndrome with her.
What if my daughter Bella could have had normal hearing simply by receiving an injection shortly after birth?
Three patients have been treated so far with no serious adverse events after six months. They have been allowed to proceed to delivering a larger dose to the next group of patients.
During that time, I have gotten an education on teenagers, an experience cast by the prism of Usher syndrome.
In the past couple of months, two papers have come across my desk that I immediately filed under “blog fodder”—reports of two new human genes that are linked to cases of Usher syndrome. This is exciting news indeed, not only because it tells us more about Usher, but because the techniques used to identify disease genes are becoming more powerful and effective all the time.
A team of researchers from multiple institutions reported a novel type of gene (CIB2) associated with Usher syndrome in the November 2012 issue of Nature Genetics.
It is not easy for a professional to deliver bad news to a family. Doctors and genetic counselors are people, too. They have parents. They have children. They understand the impact of a diagnosis like hearing loss or Usher syndrome. They don’t want to hurt or upset the family. It is human nature to try to soften the blow.
I was reading the last post from our guest blogger, Elise, and I was struck by one sentence in particular. Referring to about her son’s diagnosis, she wrote “Two weeks later, he failed the hearing test again.” To explain why that particular phrase stuck with me, let me tell you three quick stories involving some other well-meaning, kind hearted people:
Editor's Note: From time to time we invite guest bloggers to share their Usher syndrome stories and insights. Elise Faucheaux is 28 years old and currently lives in Youngsville, Louisiana with her husband Blair and their son 18 month old son Hunter. She writes regularly about her experiences raising a child with Usher on her blog, Angelic Ears and Eyes.
BioDiem has strengthened the preclinical case for its BDM-E eye disease drug with further positive results from formal studies that will help progress out-licensing opportunities for the drug. BDM-E has received Orphan Drug designation from the United States Food and Drug Administration for the treatment of the inherited degenerative eye disorder, retinitis pigmentosa.
ReNeuron, a stem cell development company in the United Kingdom, is planning to file for regulatory approval in late 2013 to launch a clinical trial of a stem cell treatment for people with retinitis pigmentosa
The above scenario is an amalgam of discussions I have had with adults with Usher. They have asked me to write about it, to let people know it exists, to let others know they are not alone.
Researchers conducting a genetic study of Old Order Amish and Mennonite populations have identified five new genes in which defects cause congenital diseases, including a previously unidentified type of Usher syndrome, type 3B.
When someone is diagnosed with Usher syndrome, there are a lot of services offered to address the physical symptoms associated with the disorder. There are hearing aids and cochlear implants, speech therapy and ASL, FMs and loops and closed captioning for hearing loss. There is mobility training and tactile sign and braille and canes and guide dogs for vision loss. There’s physical therapy, and occupational therapy, and even hippotherapy for balance issues.
The bulk of the presentations I took in today were reports from clinicians treating Usher patients. I don’t get to interact with clinicians on a regular basis, so it is hugely instructive for me to get their perspective on diagnosis and monitoring of the progressive retinal degeneration seen in Usher syndrome
Here at ARVO the last events of the day are the award lectures. Each year, several of the most impacting clinicians and scientists in the international Ophthalmology and vision research community are chosen to receive various awards and deliver a plenary lecture.
Today was an 11-hour maelstrom* of really good science. Of all the great research stories I heard, there are several that will likely be of interest to our readers:
The ARVO meeting started on Sunday, but I’ve actually been here since last Thursday to attend a pre-ARVO meeting on the topic of Retina Ciliopathies. That was an intensely focused two days, indeed. I have talked about the connecting cilium of the photoreceptor quite a bit on the blog, most recently in reviewing what we know about the molecular causes of USH1.
At last year’s ARVO conference there was a presentation reporting successful animal testing for a gene therapy product called “UshStat”*. While this work has not yet appeared in a peer-reviewed publication the ARVO abstract can be found here. The poster presentation at the meeting described the use of a non-pathogenic viral vector to deliver a normal copy of the gene affected in Usher Type 1B (MYO7A) into the retina.
In preparing to write this blog post, I planned to leap right into the meat of the study, because I know that’s what you all are most keen to hear about. However, once I got into it I realized that I’d be doing our readers a disservice by cutting to the juicy center without context.
In this last post in the series, I’ll tell you what we ultimately did to help Bella resolve her problems at school.
There have been studies done on the mental health of adults with Usher, but few on children with Usher. This study looked at 26 children in Denmark and investigated the frequency of mental and behavioral issues among the group. Published 27 March 2012.
Some of you have already noticed the little Facebook widget on the right-hand side of this page, but for those of you who haven’t, please join us in the colossal time vacuum that is social media!
My daughter Bella is thirteen years old. She is in the first year of middle school and has had a very hard time. With her permission, I have been writing about her experiences and what we did as a family to address the issues.
I'm 43 years old and smack dab in the middle of middle age. I can tell you from experience that middle age stinks. I don't see as well as I once did. I had the eyes of a hawk when I was younger. Now I need glasses. When I take Bella to one of her frequent ophthalmologist appointments, I have to squint just to read the same lines on the eye chart that she does.
"Gene therapy 'gave me sight back'" An article from the BBC about the impact of gene therapy on patients with LCA. Similar gene therapies are planned for people with Usher.
That someone will not be my daughter Bella. Well, at least I know that someone won't be Bella before she is an adult. After that, it's her call. But while it's my decision, she won't be participating in a phase I clinical trial. I'll do a lot to support Usher syndrome research, but that is just a step too far for me.
The current standard of pediatric care mandating that all newborns undergo hearing screenings has been applied successfully throughout the industrialized world. Early identification of hearing impairments gives valuable lead-time to parents and health care providers during which they can plan medical and educational interventions to improve the child's development, acquisition of language skills, and general quality of life.
My daughter, Bella, is thirteen years old and a good student. She has always loved going to school and was one of those kids that teachers described as a joy to have in class. She is even tempered and rarely gets upset.
"Researchers from the National Institute on Deafness and Other Communication Disorders and the National Eye Institute have now found that an alteration of an Usher gene that causes only deafness can preserve sight and balance when in combination with another alteration of the same gene that causes Usher syndrome, or deaf-blindness. This research has important implications for genetic counselors and may open new prospects for future therapies for vision loss."
I haven't been very active in writing for this blog recently. There are a lot of reasons involved, but the biggest has been my daughter, Bella. She's been having a tough time. I have spent a good amount of time trying to help her, which is part of the reason I have not written lately.
A Poem by Mani G. Iyer
Jennifer and Mark will be back after the holidays. Mani G. Iyer was born and raised in Bombay, India and has lived in the United States since 1985. He is deaf-blind due to Usher Syndrome. He became deaf by the age of 4, night-blind by the age of 12, and now has very little usable vision.
This study, conducted in mice modelling the human disease retinitis pigmentosa, showed that the drug norgestrel could "rescue" light-detecting retinal cells. The synthetic progestin hormone, an active component of the contraceptive "mini-Pill," allowed mice which should have gone blind to retain their sight. A new study is now planned for next year to see if humans experience the same protective effects.
"The only thing we have to fear is fear itself." - Franklin Delano Roosevelt
It's hard to believe that I am afraid of a white folding piece of aluminum, especially when there's a little rubber ball on the end of it or maybe a tennis ball. Yet the cane scares me and it should scare you, but not for the reasons you think.
The US Food and Drug Administration (FDA) has approved Oxford BioMedica's Investigational New Drug (IND) application for the Phase I/IIa clinical development of UshStat to treat Usher syndrome type 1B. Oxford Biometica will enroll 18 patients with Usher type 1b at the Casey Eye Institute in Portland, Oregon. The study will be lead by Dr. Richard Weleber.
My apologies for not posting recently, but I have excuses (yes, not a single excuse, but multiple excuses):
"I like having Usher syndrome because I have gotten to see a lot of things." - Bella Dunning
In this post, I'll introduce the molecules known to be affected in Usher patients, and begin to describe what is known about their function.
I have a friend with Usher syndrome. She worries about it. I know she does. I can see it in the way her eyes brighten when we talk about potential treatments. I can feel it in her enthusiasm for knowledge about the disease. Yet she does not live like someone who worries about Usher syndrome. She stubbornly refuses to let the future decide her present. She lives for today.
Usher syndrome is a genetically recessive condition characterized by hearing impairment--usually from birth--due to defects in the sensory neurons of the inner ear, and vision loss due to retinal degeneration, which begins to occur in childhood or adolescence and progresses through several decades.
What if Usher syndrome no longer existed? What if it went the way of Polio and Small Pox? But as with the Polio and Small Pox vaccines, this treatment would not change the fate of those of us who already have Usher syndrome. In short, we'd be the last, a people destined to be a footnote in the history books. How would you feel if no one was ever born with Usher syndrome again?
New treatment for nonsense mutations may soon be ready for use in Usher syndrome patients. A molecule known as PTC124 appears to cause the stop signal in a mutated USH1C to be ignored, allowing the protein to be formed normally in cell cultures.
Here's my somewhat belated follow up to Mark's last post regarding the unanswered questions about Vitamin A as a potential treatment for Usher syndrome.
The Coalition for Usher Syndrome Research in conjunction with the Usher Syndrome Foundation and the Decibels Foundation will be holding a third annual Usher Syndrome Family Conference this July 8th in at the Host Hotel in Sturbridge Massachusetts.
The artificial retina is the first device of its kind to move from the laboratory to the clinic, after a trial of 30 patients has shown that it can safely restore some vision to people who have lost their sight to a genetic disease.
You should take vitamin A. You should give it to your children. You should take it, of course, in a dose that is safe and prescribed by a physician, but you should take it. My daughter takes vitamin A and her vision has not changed perceptibly in the last four years.
The last day of the ARVO meeting was short and sweet, and the very last presentation I saw before heading to the Ft. Lauderdale airport was the one I'm choosing to recap here. The talk was by Hari Jayaram of the University College London's Institute of Ophthalmology, who described a collaborative research project in which cultured human retinal cells were implanted into a rat model of retinal degeneration. At first glance it might sound like the premise of a Mad Scientist thriller, but it was actually quite a well-designed and relevant study. Here's an overview of the experimental rationale, set-up, and outcome...
Today at the ARVO meeting I saw a nice poster presentation that may add a bit more data to that story. The authors, from the same research group at U Mass that produced the original patient study published in the British Journal of Ophthalmology, now report the results of dosing mice with a severe form of RP with Valproic Acid.
Today's cool Usher science story comes from Kate McCaffrey and colleagues at Rosalind Franklin University, who are making some interesting discoveries about a new potential therapy for Usher type 1C.
Today was a 12-hour juggernaut of talks, poster presentations (mine included) and really good scientific and social conversations. While many of these situations would make great blog fodder, one series of talks really had the wow factor. This session was entitled "Optogenetics, Visual Function and Restoration".
I'm here in sunny Ft. Lauderdale attending the Association for Vision Research and Ophthalmology meeting-that's right the teeming nerd hordes are at it again.
Neurotech announced in Investigative Ophthalmology and Visual Science that their NT-501 implant slowed the loss of photoreceptors in three patients, including one with Usher syndrome type 2.
My daughter has Usher syndrome because of me. She has my genes. I gave them to her. I gave her the mutation that causes a certain protein to be produced incorrectly. I am the reason she was born deaf. I am the reason she can't walk a balance beam. I am the reason her vision is getting worse.
Researchers in Japan have discovered a way to coax mouse embryonic stem cells into forming an eyelike structure.
Jennifer Phillips, Ph.D., reviewed and put together a 'FAQ' on a small observational study of the effects of Valproic Acid, which was published in the summer of 2010 online in the British Journal of Ophthalmology.
In the summer of 2010, a small observational study of the effects of Valproic Acid was published online in the British Journal of Ophthalmology1. This study reported on seven patients with autosomal dominant retinitis pigmentosa (ADRP) who were given daily doses of a drug called (in its generic form) Valproic Acid, or VPA.
Of course, when you do speak to your child about Usher syndrome, you don't want to freak them out. I can give you some guidelines on what to say, but I can't tell you the specific words or tone to take.
When should you tell your child that he/she has Usher syndrome and what, exactly, should you tell him or her?
A study published in the journal Investigative Ophthalmology and Visual Science this month reports on a study that could lay the groundwork for a clinical trial at some point in the future.
The registry idea is clearly a hit. We've gotten more comments on this posting than any other. Rather than respond to each individual comment (and since I clearly forgot some important details), I figured I would do another post with answers to the most common questions.
There are a number of treatments nearing clinical trial that could potentially help people with Usher syndrome. There are an even greater number of areas of interest that researchers think might be the source of future treatments but which are as of yet fairly unexplored.
Last night was the first of those two times that we'll skate on our home rink. My daughter Bella and my son Jack spent a couple of hours on the ice. I mean that quite literally for Bella. Jack plays hockey. Bella plays Zamboni.
I haven't been completely out of touch with the world of science, however, as I've been working long hours preparing a manuscript for submission. It's a labor of love, to be sure, combing through pages and pages of carefully laid out results, multi-panel figures, looking for opportunities to make tiny improvements and (hopefully) spotting glaring omissions before the reviewers find them.
I spend a lot of time in this blog writing about the desperation of Usher syndrome. I write about the fear that we all feel, the fear of what the disease might one day take from us. But it's the holiday season s and for today, I'd like to talk about the flip side of that fear. I want to talk about the gift of Usher syndrome.
Time passes in the research lab marked by scientific conferences, submission deadlines, and project completion. There's not much awareness of the academic calendar for those of us who don't teach regularly, but from time to time we host a new graduate student for a 12-week stint that corresponds to our academic quarter system, which tends to wake us up to the fact that we actually work at a University
QLT091001 is an orally administered synthetic retinoid replacement for 11-cis-retinal, which is a key biochemical component of the visual retinoid cycle, and is under investigation for the treatment of LCA and RP.
Molly has been a guest blogger on this site in the past and wishes to share more of her experiences. Her past posts have been among the best received on the site.
For only the second time, the Food and Drug Administration approved a company’s request to test an embryonic stem cell-based therapy on human patients. Advanced Cell Technology (ACT), based in Marlborough, Mass., will begin testing its retinal cell treatment this year in a dozen patients with Stargardt’s macular dystrophy, an inherited degenerative eye disease that leads to blindness in children.
I see all of these things, I expect them, I internalize them, but somehow I don't believe them. My little girl can't really be losing her eyesight.
Well, it's November and we are still summarizing the International Symposium on Usher Syndrome and Related Diseases that took place in May. That should be heartening for our readers. Obviously a lot happened at the conference.
Some unexpected effects of lead exposure that may one day help prevent and reverse blindness have been uncovered.
Thanks to Jennifer for carrying the blog while I procrastinated. I do have a partial excuse. I was in Denmark for a few days at the Usher Syndrome Working Group put on by Sense in conjunction with the Acquired Deaf Blindness Network conference.
To briefly summarize, there is strong experimental evidence to suggest that at least some of the time these Usher proteins physically link together to form molecular complexes that carry out some cellular functions. There are a lot of different Usher proteins involved, so understanding just the activities of those proteins has been quite challenging.
We're slowly progressing through the wealth of interesting talks at the Conference last May, and even though I didn't actually attend the Valencia meeting, I have enough familiarity with the dense molecular topics therein to give an adequate summary and their relevance to the Usher community.
'Why the heck didn't any doctor ever explain their opposition to vitamin A supplementation to me as well as Jennifer did?' I've talked to a lot of physicians that don't prescribe vitamin A, some who are strident opponents of prescribing it, and none of them explained their reasoning as clearly as Jennifer.
A new stem cell therapy is now available to eye patients using subretinal placement of adult stem cells. Initial patients included an individual with Stargardts Disease and a patient with Age Related Macular Degeneration.
I need a vacation.
Over the last 20 years or so, several studies have been conducted examining the effects of various dietary supplements on patients with progressive Retinitis Pigmentosa (RP) from a variety of causes. As a minor but important side note, these studies excluded patients with clinically diagnosed Usher type I, but did include some patients with diagnoses of Usher type 2.
First, a quick update on the Usher Syndrome Family Conference held last weekend in Seattle Washington. In a word: Awesome. Some of the leading experts in the world spoke and they all did so at a level that was possible to follow even for the recently diagnosed. They were great. It was also terrific to see so many Usher adults in attendance.
So, if we agree that change needs to happen, and that we have the power to influence this happening, let's start talking about HOW it should happen.
Julia and I recently attended our first deafblind party and I thought I'd tell you about it.
EU-funded scientists have succeeded in awakening dormant vision cones, an achievement that may lead to saving millions of people from going blind.
Dr Hanno Bolz says that his team's research challenges the traditional view that USH was inherited as a single gene disorder, and shows that it may result from at least two different genetic mutations.
This is a planned public debate between Mark Dunning and Jennifer Phillips, the two primary contributors to this blog. The ideas expressed in the posts during this debate will be purposely provocative and unfinished to invite a response from the other party. We hope you find the discussion valuable.
This is a planned public debate between Mark Dunning and Jennifer Phillips, the two primary contributors to this blog. The ideas expressed in the posts during this debate will be purposely provocative and unfinished to invite a response from the other party. We hope you find the discussion valuable.
The family conference in Seattle on July 10th is a great opportunity for families not only to connect with other families, but also to meet and talk with some of the leading researchers and Usher syndrome professionals.
The conference was enlightening and, at times, exciting. I'll give you as brief a summary of the two and half days as I can, highlighting what you really need to know.
This is a planned public debate between Mark Dunning and Jennifer Phillips, the two primary contributors to this blog. The ideas expressed in the posts during this debate will be purposely provocative and unfinished to invite a response from the other party. We hope you find the discussion valuable.
UC Irvine researchers have created a retina from human embryonic stem cells, the first time they've been used to create a three-dimensional tissue structure. The eight-layer, early stage retina could be the first step towards the development of transplant-ready retinas to treat eye disorders, such as retinitis pigmentosa and macular degeneration.
Mark began this debate by airing some grievances against the scientific and medical communities. The central charges as I read them (from my anti-hope enclave) are as follows:
At this point, since birth I had been hearing impaired. So the eye opticians asked why I was deaf, but we didn't really know, it was just unexpected. So having been at the opticians for the majority of the day, doing lots of tests, with more and more colleagues coming in to have a peek as they were all so curious.
It is also fact that while there are a number of potential treatments in development, none of those treatments have been used to successfully treat Usher syndrome. Not even in testing or clinical trials.
Usher syndrome has several types and each may have degrees of effect; for example, I was born profoundly deaf and at age 29 learned that I had the very early stages of retinitis pigmentosa.
After writing in parallel for a while about either the science or the personal impact of Usher syndrome, Jennifer and I find ourselves at the interface of these two points of view.
BOSTON—Providing retinitis pigmentosa patients with lutein plus vitamin A palmitate slowed the loss of midperipheral vision, according to a study out of the Massachusetts Eye and Ear Infirmary, Harvard Medical School (Arch Ophthalmol. 2010;128(4):403-11)
This 2010 review dives into the genetics of pathological mechanisms of Usher syndrome.
What this means for Usher syndrome: Research has come a long way since 2010!
Scientific and technological advances have, over the past couple of decades, brought us to the brink of some viable stem cell therapies for a number of human ailments. The human trials for most of these treatments are, as of this writing, still extremely preliminary, but the rate of progress makes this form of therapy a distinct possibility within the lifetime of nearly everyone reading this blog today.
University of California, Berkeley professor of neurobiology, John Flannery, is developing ways to cure genetic diseases of the retina.
Before I knew it, I was off the floor, able to go a breath, an hour, a day without fear of the future. We're now three years in to this diagnosis and the future looks less and less like it was supposed to be. I still don't like to travel without my kids. A week away still makes me nervous. I know it's unwarranted, but part of me will remain on the floor covered in orange Cheeto dust until we find a cure. But I can function now.
A research team funded by the Foundation Fighting Blindness has used cell transplantation to restore vision in a mouse model of Usher syndrome type 2A. . Never before has a cell-based treatment been used to save vision in an Usher syndrome study, in large part because no other Usher syndrome animal models have exhibited vision loss or retinal degeneration. The advancement is a critical step forward in developing a vision treatment for humans with the condition.
This article describes and compares two retinal implants, one being developed in Israel to the one in clinical trials in the U.S. by Second Sight. While they are both implants, they are also very different. Users of the Israeli one would wear just a special pair of glasses, whereas the Second Sight one includes glasses, a camera, and a processor. In addition, surgery for the Israeli one takes much less time and is less invasive. The Israeli inventors also promise much better vision. It is expected to begin clinical trials in 2013.
An international research team led by Columbia Univ. Medical Center successfully used mouse embryonic stem cells to replace diseased retinal cells and restore sight in a mouse model of retinitis pigmentosa.
Every day people search the web and find the Coalition for Usher Syndrome Research web site because they have had reason to suspect that they themselves or a family member have Usher syndrome. They do so because they know nothing about Usher syndrome and, in most cases, have never even heard of it.
Researchers have developed an implant that clears out the scar tissue of diseased retinas and seeds new ones. This quickly evolving procedure holds hope for millions of persons with retinitis pigmentosa (RP) and age-related macular degeneration (ARMD).
The video below has to be one of the best things I've ever found on YouTube. I'll spare you the long boring lecture this time, but I will preface the video by saying that it features some of my scientific role models, most notably Carl Sagan.
Still, I get a lot of questions from families about diet and its effect on the progression of Usher syndrome so it's worth discussing. It is something that intrigues a lot of researchers, but to date there has been little research done on the effect of diet on Usher syndrome.
Researchers at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts have developed a new tool for gene therapy that significantly increases gene delivery to cells in the retina.
ScienceDaily — Researchers trying to restore vision damaged by disease have found promise in a tiny implant that sows seeds of new cells in the eye.
While most of the science I've discussed on this blog so far has been fairly clinically oriented I think there's some value in spending some time getting back to the basics of the system.
Oxford BioMedica, a U.K. partner of the Foundation Fighting Blindness, has received orphan drug designation from the European Medicines Agency (EMEA) for their emerging Usher syndrome gene therapy known as UshStat. The company is planning to launch a clinical trial for UshStat in 2011. The EMEA is the European Union’s regulatory agency for medicinal products. It functions similarly to the FDA in the U.S.
You see there are no widely accepted, scientifically proven treatments for the vision component of Usher syndrome. So just about everything at this point is an opinion.
The results could have an impact on developing Usher treatments in the future. The research describing the disease progression in the mouse model adds a great deal to the understanding of what might be going on at the cellular and molecular level in the retinas of human USH2A patients.
EU-funded scientists have succeeded in awakening dormant vision cones, an achievement that may lead to saving millions of people from going blind. The dormant cones, which normally remain in the eye even after blindness has occurred, were successfully reactivated by an international team of scientists led by the Friedrich Miescher Institute in Switzerland and the Institut de la vision in France.
Less than a month ago, at the 2009 International Electron Devices Meeting (IEDM), researchers from Stanford University presented their solution for a retinal implant that has the potential to restore vision in those who lose sight due to age-related macular degeneration (AMD), retinitis pigmentosa (RP), and certain other retinal disorders. The implant is composed of solar cells embedded in a bed of flexible silicon electrodes that transfer visual images to the brain.
The man had Limbal Stem Cell Deficiency, which is not genetic, but the technology may be applicable to Usher patients in the future.
The point is that NONE of us should take the opinion of one person as gospel when it comes to treating ourselves or our children for Usher syndrome, whether that opinion is that of a trusted friend or that of a borderline science charlatan.
Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa.
The majority of my time on this blog has been spent presenting the inner workings of the scientific process: How the research world turns, why it works, how progress is measured, etc. I've been relentless in my self-appointed mission to convey to you that, in a nutshell, science is hard to do, and easy to get wrong.
A few postings ago I asked that all Usher patients and their families spend fifteen minutes a day working on Usher related activities.
Unrelated to Usher syndrome, but the successful treatment of two children with ALD, a rare genetic disease, could impact gene therapy as an RP treatment. From NPR: "This marks a high point for the field of gene therapy."
A 9-year-old boy who received gene therapy for Leber congenital amaurosis (LCA) is interviewed on CBS Morning News with his parents and Dr. Stephen Rose of the Foundation Fighting Blindness. The segment includes a before and after video of him navigating a maze.
Pennsylvania researchers using gene therapy have made significant improvements in vision in 12 patients with Leber congenital amaurosis (LCA). The findings may offer hope for those with macular degeneration and retinitis pigmentosa.
In Part I, I described the gene replacement therapy used in a pilot experiment to treat progressive retinal degeneration in LCA patients. Without rehashing the details, the major finding from this study to keep in mind is this: delivering a healthy copy of the gene via viral vector into the retinas of LCA2 patients resulted in improved vision in most of the subjects.
Researchers at Trinity College Dublin have reported the development of a new drug delivery system which has the potential to treat degenerative diseases of the retina, including retinitis pigmentosa.
A compilation of blogs written by people impacted by Usher Syndrome
A few postings ago I asked for our readers to devote fifteen minutes a day to support the cause of Usher syndrome research. I've gotten a lot of inquiries since from people interested contributing the time, but not sure what to do. In today's post and in future posts, I'll give you some ideas on how to spend your fifteen minutes.
The Dunning's daughter, Annabella, has Usher syndrome. The rest of the family does not but they are no less effected by it. Even with the diagnosis, life still goes on and it's mostly unintentional comedy. Usher syndrome stinks, but you need a little fertilizer if you want to grow roses. Read all about it here.
New York Times article outlining a number of experimental treatments being tested to help restore vision. An intensive three-year research project involving electrodes surgically implanted in the eye, a camera on the bridge of the nose and a video processor strapped to the waist is part of a burst of recent research.
The research I want to share with you involves gene therapy for another retinal disease that shares some similarities with Usher syndrome.
Led by electrical engineering professor John Wyatt, team develops retinal implant that could help restore useful level of vision to certain groups of blind people. Inspired by the success of cochlear implants that can restore hearing to some deaf people, researchers at MIT are working on a retinal implant that could one day help blind people regain a useful level of vision.
While I'm putting the finishing touches on that opus, I just want to briefly respond to Mark's last post, specifically regarding the relative expertise and motivation of Usher researchers vs. parents, siblings, teachers, social workers, mentors, or other members of the support network surrounding an individual with Usher syndrome.
Report on efforts of a team in Germany to develop an electronic retinal prosthesis.
But the truth is that we, you and I, hold the truly important titles. Being a Da.D. or an Mo.m. or having Us.h. makes you the unquestioned expert on Usher syndrome.
Among the many symptoms of Usher syndrome is guilt. Parental guilt, that is.
The degree to which any single finding might impact the field is largely informed by the context provided by the other data points surrounding it, which can lend support, relevance and strength to the conclusion.
I find the weather to be a lot like Usher syndrome. It's this big mystery that I have no control over that affects my life every day
In the next few posts, I'm planning to present an overview of biomedical research, and I'll begin by discussing the general flow of information from the laboratory bench to the patient.
First up is why funding organizations would be wise to invest in projects aiming to improve early diagnosis of Usher syndrome.
Greetings to all, and a big thank you to Mark for inviting me to contribute to his Usher Syndrome Blog. My name is Jennifer Phillips, and I am a research biologist specializing in molecular cell biology of Usher syndrome.
I'm no longer alone. Starting tomorrow I'll be joined regularly by Jennifer Phillips.
I was a well educated, even tempered parent receiving expected information about my daughter in the best possible manner and I was still crushed.
I am not a writer. I am not a doctor. I am not an expert. I am just the father of a 10 year old girl with Usher syndrome.
One of the neglected aspects of Usher syndrome are the balance issues associated with Usher syndrome type 1. These are forgotten because 1) vestibular abnormalities are not associated in all types of Usher and 2) compared to the other symptoms of Usher syndrome (hearing loss/retinitis pigmentosa), balance on the surface is a relatively benign problem
Physicians worry about an Usher diagnosis. They know the emotional impact of the diagnosis on the family and those not intimately familiar with Usher know only that there is no cure. So they worry that a diagnosis of Usher syndrome might actually do more harm to a family than good.
In short, there is something that can be done. Lots of somethings. But you need the diagnosis and you need it as early as possible. Here's just some of the reasons why early diagnosis is a good thing for a family:
A new clinical test called the OtoChipTM Test for Hearing Loss and Usher Syndrome was launched by the Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine on June 22, 2009. This test sequences ~70,000 bases of DNA across 19 genes involved in hearing loss and Usher syndrome.
We need to identify all types of Usher syndrome as early as possible for the sake of the families.
To sign or not to sign is still the question before us, only this time we'll look at not to sign. This is generally represented by the Auditory Verbal Therapy approach.
To sign or not to sign is still the question before us, only today we'll talk about American Sign Language (ASL) as a management option for Usher Syndrome. Historically, this has been more than just ASL for people with Usher. Eventually, as their vision degrades, people with Usher who had used visual ASL turn to tactile sign. There are a number of different variations on tactile signing, but for most people with Usher it means one of two things.
To sign or not to sign, that is the question today, and it's a big one when we're talking about Usher syndrome. It's big enough that I spent nearly two weeks trying to find a way to express my opinion on the subject that wouldn't offend, well, pretty much everyone. Nothing is more polarizing in the Usher community or the Deaf community as a whole.
Neurotech Pharmaceuticals, Inc., today announced that the Company's product candidate, NT-501 demonstrated a strong biologic effect in two Phase 2 clinical trials for retinitis pigmentosa (RP)
One of the topics of discussion at the conference was the emotional toll of an Usher diagnosis, particularly at a young age, and it's effects on our ability to identify children as early as possible.
The meeting was attended by a dozen researchers and a couple of observers. The goal of the meeting was to try to support the many upcoming clinical trials on Usher syndrome.
Very little research-based information exists about the benefits and challenges of cochlear implants for children who are deaf or hard of hearing, who also have a vision impairment. A new study aims to remedy that. This multi-year project will address a number of objectives to begin to provide a research base for more informed decision-making by families and service providers, in relation to cochlear implants for children who are deaf-blind.
A dozen of the leading Usher syndrome researchers will be meeting in Boston on May 12th. It's a small group, but that's a good thing because the goal is to come out with some recommendations to present to the larger community.
What can I do to help my child? That's the first thing parents ask when their child is diagnosed with Usher syndrome. Given that there are no accepted treatments for Usher syndrome at the moment, parents are often encouraged, with the best of intentions, to support research.
One of the hopes of the Usher Syndrome Coalition is to create a community of families, researchers, caregivers, and fund raisers.
I'll post notes on what I hear and what I know about Usher syndrome research and hopefully that brings a little light in to lives of those coping with the diagnosis. We could all use a little hope.
The transplantation of stem cells that are capable of producing functional cell types might be a promising treatment for hearing impairment.
It has been discovered that a myosin protein connected to Usher syndrome works differently from many other myosins.
This handbook on stem cell therapies was published in 2008 but is still very relevant today.
According to Reuters, stem cells from tiny embryos can be used to restore lost hearing and vision in animals. This research holds promise for humans.
Aminoglycocides have shown promising effects in cell cultures and may someday be used to suppress mutations involved in Usher syndrome.
The Coxsackievirus and Adenovirus Receptor (CAR) is an essential regulator of cell growth and adhesion during development. The gene for CAR, CXADR, is located within the genetic locus for USH1E. Based on this and a physical interaction with harmonin, the protein responsible for USH1C, researchers hypothesized that CAR may be involved in cochlear development and that mutations in CXADR may be responsible for USH1E.
What this means for Usher syndrome: We have potentially identified CXADR as the gene responsible for USH1E.
By Ilene Miner, CSW and Joe Cioffi, M. Ed. Published by Helen Keller National Center, this study looks at early intervention or involvement of the person with the disability in the process of problem solving, introducing role models, and encouraging the student to take care of him or herself and make independent decisions, which is rarely implemented in work with children, youth, and young adults with Usher syndrome.