These clinical trials and natural history studies have the potential to benefit people with Usher syndrome.
Each research project listed below will include a graphic of the research continuum. The gold box indicates where this project falls on the continuum, illustrating its progress towards reaching people living with Usher syndrome, from "Bench to Bedside."
Gene-Independent Clinical Trials
This study will test whether taking NAC long-term can slow the progression of vision loss in a person with RP. N-acetylcysteine is a strong antioxidant that is FDA-approved for acetaminophen (paracetamol) overdose.
A Phase 1 clinical trial of Nacuity’s GMP-grade NPI-001 solution in healthy volunteers was completed with no serious adverse events. A randomized, placebo-controlled, double-masked, multicenter, Phase 1/2 clinical trial of Nacuity’s proprietary NPI-001 tablets, the SLO-RP Study, is enrolling patients with RP associated with Usher syndrome.
Nanoscope Therapeutics reported positive top-line phase 2b data in Q1 2023 and is engaging the FDA and EMA on a path to approval.
Dose Escalation Study to Evaluate the Safety/Tolerability and Efficacy of EA-2353 in Subjects With Retinitis Pigmentosa
On May 4, 2023, Endogena announced it had completed patient enrollment ahead of schedule in its Phase 1/2a trial of EA-2353 for the treatment of retinitis pigmentosa (RP). With the dose-escalation stage completed, the ongoing trial is now in the expansion cohort stage.
jCell is a first-in-class allogeneic cell therapy in late-stage clinical development for retinitis pigmentosa. Phase 2b results announced in July 2020 showed that jCell therapy had promising efficacy and was well tolerated in patients. Based on these encouraging results, jCyte is excited to move toward a pivotal trial as soon as possible.
Cedars Sinai, a non-profit healthcare organization based in Los Angeles, has received authorizations 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 RP. The trial is being funded by a $10.5 million grant from the California Institute for Regenerative Medicine. The study's principal investigator is Clive Svendsen, PhD, professor of Biomedical Sciences and Medicine and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute.
Natural History Studies
This "Natural History Study in Subjects With Usher Syndrome" sought to evaluate the natural progression of disease over time in 50 USH1B patients in Italy, Spain and the Netherlands.
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants (Uni-Rare)
Jennifer Lentz, Ph.D. and her team at the Neuroscience Center of Excellence, LSU--New Orleans are recruiting patients for three Natural History studies on Usher syndrome: 1) Usher Syndrome in Louisiana Natural History Study; 2) Prospective Natural Study of Vision Loss in USH 1C: A Multicenter Study; 3) Prospective Natural History Study of the Loss of Balance in USH 1C
The Usher 1F Collaborative, a family-founded nonprofit, and the Foundation Fighting Blindness partnered to launch a natural history study, “Rate of Progression of PCDH15-Related Retinal Degeneration in Usher Syndrome 1F (RUSH1F).”
This four-year natural history study, "Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A)" was sponsored by the Jaeb Center for Health Research, funded by the Foundation Fighting Blindness and completed in April 2023.
From 2015 to 2021, the LIGHT4DEAF study on Usher syndrome was conducted in France, coordinated by Professor José-Alain Sahel. This five-year natural history study of Usher syndrome aims to look at the functional and structural parameters for retinal, auditory and vestibular impairments that happen overtime. This will allow researchers to document the natural history of Usher syndrome and establish clinical endpoints that may be useful for future clinical trials.
Interventional Trials (Devices)
Dr. Shuman He at Ohio State University and the National Institute on Deafness and Other Communication Disorders (NIDCD) began enrolling an estimated 44 participants in July 2021. Participants will have either Usher syndrome (USH) or idiopathic hearing loss. USH causes deterioration of the cochlear nerve (CN). This study hopes to create evidence-based therapies for cochlear implant patients with USH. The researchers' goals are to study neural health and how neurons represent temporal and spectral cues in implanted patients with USH. “Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.”
Clinical Trials and Natural History Studies - Related Science News
Nanoscope Therapeutics Inc., a clinical-stage biotechnology company, has recently announced that one of its drugs is approved for Phase 2b clinical trial.
Researchers from Sun Yat-sen University are attempting to test the efficacy and safety of oral minocycline for the treatment of retinitis pigmentosa (RP). Minocycline, a second generation, semi-synthetic tetracycline antibiotic, a highly lipophilic molecule and can easily pass through the blood-brain barrier. Several clinical trials and animal experiments have reported that minocycline exert anti-apoptotic, anti-inflammatory and antioxidant effects in treating neurodegenerative diseases. They have proposed to test the effect and safety of oral minocycline for RP.
What this means for Usher syndrome: If clinical trials are successful, Usher patients will have the possibility to be included in this non-invasive therapy to prevent photoreceptor cell death.
GenSight Biologics, a biopharma company focused on discovering and developing gene therapies for retinal neurodegenerative diseases and central nervous system disorders, announced that the independent Data Safety Monitoring Board (DSMB) has completed its first safety review of the ongoing PIONEER Phase I/II clinical trial of GS030 combining gene therapy and optogenetics for the treatment of Retinitis Pigmentosa (RP). No safety issues have been found for the first cohort of subjects who received a single intravitreal injection of 5e10 vg combined with a wearable optronic visual stimulation device. Therefore, the DSMB has recommended moving forward with the plan without any modification to the protocol and recruiting the second cohort of subjects to receive an escalated dose of 1.5e11 vg.
What this means for Usher syndrome: This clinical trial could lead to a treatment for RP and may be applicable to Usher syndrome.
ReNeuron Group plc has announced the latest updated positive preliminary results in the company’s ongoing phase 1 and 2a clinical trial of its human retinal progenitor cell (hRPC) therapy candidate in retinitis pigmentosa. All three subjects in the first group of phase 2a have demonstrated a sustained and further improvement in vision compared to their pre-treatment baseline.
What this means for Usher syndrome: This potential therapy could provide a means to restore lost vision in Usher syndrome patients.
ProQR Therapeutics N.V., a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, today announced the first patient treated in the Phase 1/2 STELLAR clinical trial for QR-421a in patients with Usher syndrome type 2 or non-syndromic retinitis pigmentosa (RP). Interim data from the trial are expected to be announced by mid-2019. According to David G. Birch, Ph.D., Principal Investigator of STELLAR and Scientific Director of the Retina Foundation of the Southwest in Dallas, Texas, “The STELLAR study is one of the first studies of its kind exploring the impact of ProQR’s RNA therapies on patients with Usher syndrome type 2 due to an Exon 13 mutation. The STELLAR trial will explore whether QR-421a (ProQR’s RNA therapy) can slow disease progression or even reverse it.”
What this means for Usher syndrome: There may be a potential drug available to reverse blindness caused by Usher syndrome.
ProQR Therapeutics announced that the FDA has cleared the Investigational New Drug (IND) application for QR-421a. QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of the vision loss associated with Usher syndrome type 2 and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. ProQR plans to start enrolling patients in a Phase 1/2 trial named STELLAR in the coming months with preliminary data expected in mid-2019.
ProQR Therapeutics N.V. announced the results for their clinical trial of QR-110 LCA 10 is on track, and eight out of twelve patients have been enrolled in a Phase 1/2 trial. The results for safety and efficacy for the trial are expected to be announced in the second half of 2018. Currently, they planing to announce data from a QR-421 study for Usher Syndrome. The organization has received $7.5 million in funding from the Foundation Fighting Blindness (FFB) and hopes to use QR-421a for Usher Syndrome Type 2A to target mutations in exon 13.
ReNeuron, a developer of cell-based therapeutics, received a $1.5 million grant award from the UK Innovations agency. The project will allow further development of cell banks of ReNeuron’s hRPC candidate and as well as the development of product release assays for late-stage clinical development. The hRPC therapy is currently being tested in a Phase III clinical trial in the US for patients suffering retinitis pigmentosa.
GenSight Biologics, a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, announced UK Medicines and Healthcare Regulatory Agency (MHRA) acceptance of the Company’s Clinical Trial Application (CTA) to initiate the PIONEER Phase I/II study of GS030 in patients with Retinitis Pigmentosa (RP).
jCyte, one of the leaders in developing cell-based therapies for RP, announces positive 12-month results from its Phase 1/2a clinical trial to treat retinitis pigmentosa with stem cells.
Encouraging signs this week that the FDA is serious when it granted Regenerative Medicine Advanced Therapy (RMAT) status to the CIRM-funded jCyte clinical trial for a rare form of blindness. This is a big deal because RMAT seeks to accelerate approval for stem cell therapies that demonstrate they can help patients with unmet medical needs.
Our latest USH Talk features researcher Dr. Jacque Duncan from the University of California, San Francisco. Dr. Duncan shares an overview of an upcoming clinical trial that aims to study the rate of progression of USH2A related retinal degeneration: The RUSH2A Study.
Three patients have been treated so far with no serious adverse events after six months. They have been allowed to proceed to delivering a larger dose to the next group of patients.
The US Food and Drug Administration (FDA) has approved Oxford BioMedica's Investigational New Drug (IND) application for the Phase I/IIa clinical development of UshStat to treat Usher syndrome type 1B. Oxford Biometica will enroll 18 patients with Usher type 1b at the Casey Eye Institute in Portland, Oregon. The study will be lead by Dr. Richard Weleber.