Breaking the Silence, Lighting the Dark: Innovations in Usher Syndrome Treatment

Abstract

Usher Syndrome is an autosomal recessive disorder and the leading cause of combined deafness and blindness worldwide. It affects 25,000 people in the United States and 400,000 people worldwide (Usher Syndrome Coalition; U.S. Department of Health and Human Services). It is characterized by congenital hearing loss and progressive vision impairment due to retinitis pigmentosa. The condition is caused by mutations in several genes, such as MYO7A, USH2A, and CLRN1 (U.S. National Library of Medicine, MYO7A Gene; U.S. National Library of Medicine, USH2A Gene; U.S. National Library of Medicine, CLRN1 Gene). Conventional treatments, such as cochlear implants, low-vision aids, and speech therapy, often help mitigate the symptoms but do not repair the underlying genetic basis of the disease. In this article, the potential of gene therapy as a breakthrough treatment for Usher Syndrome will be assessed. The in vivo gene therapy approach enables the introduction of corrective genetic materials into Usher Syndrome patients using viral or non-viral vectors. Advances in gene therapy, such as dual Adeno-Associated Virus (AAV), allowed for the delivery of larger genes such as MYO7A, allowing for partial function restoration in preclinical models. Antisense oligonucleotides (ASOs), especially QR-421a, have shown potential in manipulating USH2A mutations with RNA splicing, with encouraging results in early-phase clinical trials. Human trials for this therapy approach, including the LUCE-1 Phase 1/2 and LUNA Phase 2b, are currently proving safety and efficacy. Although challenges such as immune response, gene size limitations, and delivery accuracy persist, advancements in vector design engineering, CRISPR editing, and precision medicine provide hope for curative therapies. Future treatments can benefit from combining gene therapy with stem cell regeneration and neuroprotective pharmacology to achieve optimal long-term outcomes. Overall, gene therapy remains a promising approach to not only managing but also reversing symptoms of Usher Syndrome, giving a personalized approach to treatment.