Usher syndrome is the most common genetic cause of combined deafness and blindness. More than 400,000 people are affected by this worldwide. There is currently no cure for Usher syndrome, but there is a growing USH community.
The mission of the Usher Syndrome Coalition is to raise awareness and accelerate research while providing information and support to individuals and families affected by Usher syndrome. We strive to be the most comprehensive resource for the Usher syndrome community, bridging the gap between researchers and families. Learn more and get involved.
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.
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.
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