Usher Syndrome Blog and News
The latest USH blog posts and various news items impacting the Usher syndrome community. Join our mailing list.
Retinitis pigmentosa (RP) is a rare genetic disease that causes loss of photoreceptors, which are the light sensitive cells in the retina. This disease can lead to blindness and affects more than 2 million people worldwide. In a groundbreaking clinical trial led by Paris-based GenSight Biologics, a man who was blind for 40 years successfully regained some visual function with a technique called optogenetics. Optogenetics uses light to control neuron activity. In this study, a light-sensing protein called ChrimsonR was injected into the eye and delivered to the patient’s retinal cells. After a four-month period to allow his body to make ChrimsonR protein, the patient was fitted with special goggles that detect and shift incoming light into a specific color range. The patient was able to see high-contrast images and objects, and his brain activity was the same as someone with normal sight.
What this means for Usher syndrome:
More patients will need to be enrolled and evaluated, but if this study proves to be successful, RP patients who are blind may be able to regain some sight, increasing their quality of life. Because vision loss in Usher syndrome is a type of RP, this therapy may also be beneficial for Usher syndrome patients.
An overview of the USH2021 Connections Conference agenda, the annual global gathering of the Usher syndrome community.
The Usher Syndrome Coalition's 2021 virtual USH Connections Conference will be more accessible than ever. Now offering Spanish spoken language interpreting for all sessions, plus on-screen captioning and American Sign Language (ASL) interpretation.
Estamos felices de anunciar que la Conferencia Virtual Conexiones USH 2021 organizada por el Usher Syndrome Coalition va a ser más accesible que nunca.
Sumado a los subtítulos en pantalla e interpretación de Lenguaje de Señas Americano (ASL), vamos a ofrecer traducción hablada en español para todas las sesiones.
During our USH2021 program, those living with Usher syndrome will take center stage as the experts. There will be something for everyone in the Usher syndrome community. Join us!
Check out some of the special programming made possible by our USH Partners. A detailed agenda will be available in the coming weeks.
Researchers inject patients' retina with own platelet rich plasma as possible treatment option.
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.
Photoreceptor precursor cells that were generated from stem cells were able to be successfully transplanted into the retina and demonstrate basic visual function.
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.
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.
A type of laser light therapy called photobiomodulation shows promising results in the ability to preserve retinal performance, structure and function.
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.
Congressman James P. McGovern of Massachusetts in the House of Representatives recognizes Usher syndrome, the Usher Syndrome Coalition and Usher Syndrome Awareness Day.
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.
Mark Dunning, founder of the Usher Syndrome Coalition steps down from the Board of Directors and warmly welcomes long-time supporter Lanya McKittrick, Ph.D., as the new chair of the Usher Syndrome Coalition.
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.
The Usher Syndrome Coalition has been closely monitoring the rapidly evolving coronavirus (COVID-19) situation, while listening to speaker and attendee concerns. The Coalition’s Board of Directors and staff have made the difficult decision to postpone the in-person USH Connections Conference and to hold a virtual event in its place this July 2020.
Originally planned for July 10-11, 2020 at the Omni Austin Hotel at Southpark, the venue has been incredibly accommodating, offering us the opportunity to postpone the event to the same time next year, July 9-10, 2021.
Please join our Hearts on Hand outreach campaign to inform, reach out and provide virtual support to our USH Family during this difficult time.