Usher Syndrome Blog and News
The latest USH blog posts and various news items impacting the Usher syndrome community. Join our mailing list.
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 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.
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.
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.
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.
Allergan, global pharmaceutical company, and Editas Medicine, a genome editing company, have announced the treatment of the first patient in the BRILLIANCE clinical trial of AGN-151587 (EDIT-101) at Oregon Health & Science University (OHSU) Casey Eye Institute. AGN-151587 is an experimental medicine delivered via sub-retinal injection under development for the treatment of Leber Congenital amaurosis 10 (LCA10), an inherited form of blindness caused by mutations in the centrosomal protein 290. The BRILLIANCE clinical trial is a Phase 1/2 study to evaluate AGN-15187 for the treatment of patients diagnosed with LCA10 and is the world’s first human study of an in vivo, or inside the body, CRISPR genome editing medicine. The trial will 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, it will provide proof of principle for use in other forms of blindness including Usher syndrome.
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.
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.
In this USH Talk, Marcia Brooks shares an overview of iCanConnect, the National Deaf-Blind Equipment Distribution Program. iCanConnect provides free equipment and training to people with both significant hearing and vision loss who meet federal disability and income eligibility guidelines. iCanConnect is a national program with local contacts.
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.
The Usher Syndrome Coalition is soliciting speaker abstracts for research-based presentations for the full-day general session of the 12th Annual USH Connections Conference, taking place Saturday, July 11, 2020 at the Omni Austin Hotel at Southpark in Austin, Texas.
Potential topics for research-based presentations include, but are not limited to: Science, Assistive Technology, Social and Emotional Support, Advocacy.
The Usher Syndrome Coalition is partnering with Fondation Pour l'Audition and Fondation Voir et Entendre to organize the International Usher Info Symposium that will take place in Paris on June 26th-27th, 2020. This event is entirely dedicated to Usher syndrome. It will gather outstanding experts and actors (ENTs, ophthalmologists, residents, young scientists, students, patient associations) in the field of sensory disorders.
Angela Anker describes her experience at the 2019 Usher Syndrome Coalition USH Connections Conference held in Philadelphia this past July. This conference provides an opportunity for those impacted by Usher Syndrome to learn about the latest developing treatments from leading USH researchers while connecting with hundreds of impacted individuals, their families, and professionals serving the DeafBlind community. There were over 300 attendees.
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).
LSU Health New Orleans and the University of Louisiana, Lafayette present this community-wide program to learn more about Usher syndrome in Louisiana, and what is being done to help those living with Usher. After the symposium, there will be a special opportunity for individual sessions with Dr. Jennifer Lentz to sign up for studies and genetic testing.
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.