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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.
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.
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.
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.
The Scientific and Medical Advisory Board of Retina International recommends that those affected by an underlying retinal dystrophy do not self-medicate with chloroquine and strongly advises patients to follow the advice of their healthcare provider prior to any use of chloroquine. It is still unclear how chloroquine or any antimalarial drug would work against COVID-19.
Chloroquine is an antimalarial drug that was FDA approved in 1934. Since then it has been found to be beneficial for the treatment of autoimmune diseases such as lupus or rheumatoid arthritis. The standard doses of chloroquine used for the treatment of malaria and other diseases have few side effects. However, toxicity is encountered when high doses are injected very rapidly into the bloodstream (parenterally) or taken as tablets (orally) in regular doses over many years. Patients with underlying retinal disease may be at higher risk for chloroquine toxicity. The most serious complications of chloroquine are retinopathy, cardiomyopathy, neuromyopathy and myopathy. The retinopathy is encountered with the prolonged use of chloroquine that can lead to irreversible damage to the retina and the loss of vision. Chloroquine toxicity is of serious concern for the retina because it is not treatable. Additionally, there have been cases of progressive vision loss in patients even years after the treatment by chloroquine or hydroxychloroquine.
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.
There are hundreds of millions of rare disease patients, half of them children, whose conditions are not getting enough funding for research and treatment. However, by banding together, the patients are changing how the medical community responds to their diseases. A highly organized group of patients can play a pivotal role in accelerating medical research. The need is immense. Similar to cystic fibrosis, many rare diseases are deeply debilitating, if not deadly. Individually they are rare but are remarkably common. Roughly about 25-30 million Americans are living with a rare disease and roughly 400 million worldwide.
What this means for Usher syndrome: It is important that those of us who are living with Usher syndrome continue to spread awareness and advocate for research on Usher syndrome.
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).
ProQR Therapeutics N.V. (Nasdaq:PRQR), a company dedicated to changing lives through the creation of transformative RNA medicines for severe genetic rare diseases, announced today its participation in the Foundation Fighting Blindness My Retina Tracker Program, a collaborative, open access program run by Blueprint Genetics and InformedDNA providing no-cost genetic testing and genetic counseling for individuals with a clinical diagnosis of an inherited retinal disease (IRD) such as Leber’s congenital amaurosis (LCA) and Usher syndrome, amongst others.
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.
Biblical references aside, restoring vision to the blind has proven to be a major technical challenge. In recent years, considerable advances have been made towards this end, especially when retinal degeneration underlies the vision loss such as occurs with retinitis pigmentosa. Under these conditions, optogenetic therapies are a particularly promising line of inquiry where remaining retinal cells are made into "artificial photoreceptors". However, this strategy is not without its challenges and a model system using human retinal explants would aid its continued development and refinement. Here, we cultured post-mortem human retinas and show that explants remain viable for around 7 days. Within this period, the cones lose their outer segments and thus their light sensitivity but remain electrophysiologically intact, displaying all the major ionic conductances one would expect for a vertebrate cone. We optogenetically restored light responses to these quiescent cones using a lentivirus vector constructed to express enhanced halorhodopsin under the control of the human arrestin promotor. In these 'reactivated' retinas, we show a light-induced horizontal cell to cone feedback signal in cones, indicating that transduced cones were able to transmit their light response across the synapse to horizontal cells, which generated a large enough response to send a signal back to the cones. Furthermore, we show ganglion cell light responses, suggesting the cultured explant's condition is still good enough to support transmission of the transduced cone signal over the intermediate retinal layers to the final retinal output level. Together, these results show that cultured human retinas are an appropriate model system to test optogenetic vision restoration approaches and that cones which have lost their outer segment, a condition occurring during the early stages of retinitis pigmentosa, are appropriate targets for optogenetic vision restoration therapies.
What this means for Usher syndrome: For Usher patients, this means that there is a therapeutic window during which cones can be “rescued” from dying and their “normal” activity restored. Although still too premature, this type of treatment in combination with strategies to correct the mutated Usher protein will help to slow or even stop the progression of the disease.
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.