Usher Syndrome Research Advances

AAVANTGARDE BIO’S DUAL-VECTOR USH1B GENE THERAPY MOVES INTO PHASE 1/2 CLINICAL TRIAL

AAVantgarde Bio, a gene therapy development company based in Italy, has dosed the first patient in its Phase 1/2 retinal gene therapy clinical trial for people with Usher syndrome type 1B (USH1B) which is caused by mutations in the gene MYO7A. Known as LUCE-1, the trial is taking place at the University Hospital of Campania “Luigi Vanvitelli” (Naples, Italy) with Prof. Francesca Simonelli serving as lead investigator. Two additional sites for the Phase 1/2 trial in the UK will be announced. The company plans to launch sites in the US if the emerging gene therapy moves into a pivotal, Phase 3 trial. Fifteen patients ranging from 18 to 50 years of age will be enrolled in the Phase 1/2 trial. Three doses of the USH1B gene therapy will be evaluated.

Known as AAVB-081, the gene therapy is the first clinical application of a dual-vector gene delivery system for a retinal disease. AAVB-081 uses an adeno-associated virus (AAV), which works like a vast container system, to deliver healthy copies of the MYO7A gene into retinal cells. 

Because the MYO7A gene is too large for a single AAV container, the gene is split into two halves and delivered in two containers. Once in the cell, the halves are recombined. The one-time treatment is contained in a tiny drop of liquid that is injected underneath the retina.

 

SAFETY CLINICAL TRIAL LAUNCHED FOR USH3A DRUG

A Phase I clinical trial has been launched in Perth, Australia, to evaluate the safety and tolerability of an emerging oral drug known as BF844 for the treatment of Usher syndrome type 3 (USH3). The clinical trial will also evaluate the drug’s pharmacokinetics, i.e., how the drug is metabolized and distributed throughout the body. The trial will be completed in September 2025.

 

THÉ­A LAUNCHES SEPUL BIO TO ADVANCE LCA10 AND USH2A RNA (ANTISENSE OLIGONUCLEOTIDE) THERAPIES

Théa has launched a new business unit, Sepul Bio, to continue clinical development of two RNA therapies: sepofarsen for people with LCA10 caused by the IVS26 mutation in the CEP290 gene and ultevursen for people with exon 13 mutations in the USH2A gene. Both therapies, originally developed by ProQR, had shown efficacy in earlier clinical trials. In December 2024, SepulBio announced that it had dosed the first patient in its LUNA Phase 2b clinical trial for ultevursen. Details on the clinical trial for sepofarsen are forthcoming.

 

PHASE 3 CLINICAL TRIAL OF NAC LAUNCHED FOR RP PATIENTS

Johns Hopkins University (JHU) has launched a Phase 3 clinical trial of N-acetylcysteine (NAC) for the treatment of retinitis pigmentosa (RP). Known as NAC Attack, the 45-month study is enrolling approximately 438 patients at 30 sites throughout the US, Canada, Mexico, and Europe. Study participants will be assigned randomly 2:1 to either the treatment or placebo group, respectively. If the NAC group shows benefit (i.e., slowing of vision loss) at 21 months, participants in the placebo group will begin to receive the treatment.

JHU’s Peter Campochiaro, MD, and Xiangrong Kong, PhD, designed the trial and are its lead investigators.

The National Eye Institute is providing more than $20 million in funding for NAC Attack.

NAC is an oral antioxidant approved in 1963 by the US Food & Drug Administration for acetaminophen (Tylenol®) overdose.  It is also used for treating cystic fibrosis and pulmonary diseases.

 

NACUITY CONDUCTING CLINICAL TRIAL FOR ORAL ANTIOXIDANT THERAPY

Dallas-based Nacuity has launched a Phase 1/2 clinical trial in Australia for its oral antioxidant therapy. The trial is for people with Usher syndrome. The Foundation Fighting Blindness is investing up to $7.5 million to advance the promising, emerging drug for retinitis pigmentosa, Usher syndrome, and related conditions. Known as N-acetylcysteine-amide (NACA), the molecule is designed to slow vision loss by protecting retinal cells from oxidative stress. In previous Foundation-funded lab studies at Johns Hopkins University, NACA slowed retinal degeneration in rodent models of RP.

 

FOUNDATION FIGHTING BLINDNESS CONDUCTING RUSH2A NATURAL STUDY FOR PEOPLE WITH USH2A MUTATIONS

The Foundation Fighting Blindness has launched a natural history study for people with mutations in the USH2A gene, which are leading causes of Usher syndrome and retinitis pigmentosa. A major goal of the study, known as RUSH2A, is to better understand the course of vision loss in people with USH2A mutations, so that researchers can design successful clinical trials for potential therapies and identify patients for the treatment studies. More than 100 patients are enrolled at approximately 20 sites in the US, Canada, and Europe.

 

FOUNDATION LAUNCHES USH1F NATURAL HISTORY STUDY

The Foundation is partnering with the Usher 1F Collaborative, a family-founded nonprofit driving research for Usher syndrome type 1F (USH1F), to launch a natural history study, the Rate of Progression in PCDH15-Related Retinal Degeneration in Usher Syndrome 1F (RUSH1F). Additional funding for the project will be provided by the Marjorie C. Adams Trust. USH1F is a subtype of Usher syndrome caused by mutations in the gene PCDH15.

 

ATSENA THERAPEUTICS DEVELOPING USH1B GENE THERAPY

Atsena Therapeutics is developing a dual vector AAV gene therapy for people with mutations in MYO7A, the gene, when mutated, causes Usher syndrome 1B. The Foundation is funding Atsena through its RD Fund, a venture philanthropy fund for emerging therapies in, or moving toward, clinical trials.

 

 

APRIL 2025