Update on Gene Therapy Clinical Trials for Eye Diseases.

Abstract

Inherited and complex retinal degenerative diseases, such as retinitis pigmentosa, age-related macular degeneration, and glaucoma, represent a significant global burden of irreversible vision loss. Due to immense genetic and clinical heterogeneity and complex underlying mechanisms, these diseases still lack safe and effective disease-modifying treatments. This review summarizes the current landscape of gene therapeutic approaches to develop novel treatments for these blinding conditions. Specifically, we provide an update on several ongoing or completed clinical trials on gene-specific or gene-agnostic approaches, including recombinant adeno-associated viral vector-mediated delivery of the full gene or gene editing and antisense oligonucleotide components into the eye. We also discuss the initial clinical trial results of the use of the different approaches to ocular delivery, including subretinal, intravitreal, and suprachoroidal delivery. While long-term clinical trial data and refined clinical endpoints are essential to assess the efficacy, safety, and durability of these strategies, the data so far underscore the immense potential of gene therapy to revolutionize the management of retinal diseases in patients living with these debilitating conditions.