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Usher Syndrome Blog and News

The latest USH blog posts and various news items impacting the Usher syndrome community. Join our mailing list.

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.

The Usher Syndrome Coalition is closely monitoring ongoing developments in the coronavirus (COVID-19) spread.
The Usher Syndrome Coalition’s Board of Directors is evaluating the status of our annual USH Connections Conference, with the guidance of up-to-date information released by the Centers for Disease Control and Prevention (CDC) and other advisories within the United States and worldwide. Decisions will be communicated to all of our contacts immediately.

Please join our Hearts on Hand outreach campaign to inform, reach out and provide virtual support to our USH Family.

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 .

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.

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.

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.

How do you keep up to date on current research related to your specific Usher mutation? This is a hub for all Usher syndrome research updates, including progress information for each subtype, cell-based therapy approaches, current clinical trials, natural history studies and relevant publications. 

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.

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.

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.

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.

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