Medical Genetics in Ophthalmology: Through the Lens of Genetics-Informed Therapies OnDemand-Ocular Gene Therapy Landscape: Past and Future

Video Transcription

Video Summary

Dr. Tomas Almon from Penn presents an overview of ocular gene therapy for retinal degenerations, highlighting progress and challenges. Over 20 years, hundreds of gene therapies have shown promise in animal and cellular models, with numerous clinical trials underway. However, only one treatment (for RPE65-associated LCA) has been approved, revealing a bottleneck in translating research to effective therapies. Dr. Almon emphasizes the complexity of retinal diseases, where preserved retinal structure doesn’t always correlate with visual function. Gene therapy can improve retinal function but may not halt degeneration entirely, necessitating combined therapeutic approaches. Examples include treatments targeting RPE diseases (RPE65-LCA), phototransduction defects (GUCY2D-LCA), ciliopathies (CEP290-LCA), and severe degeneration (LCA5), employing gene augmentation, antisense oligonucleotides, and gene editing. He urges the field to adopt more flexible clinical trial designs and mechanistic outcome measures beyond visual acuity to better capture therapeutic impact. Optimism remains for future success, especially with early intervention in young patients before degeneration onset.

Asset Subtitle

Tomas S. Aleman, MD

Keywords

ocular gene therapy

retinal degenerations

RPE65-LCA

gene editing

clinical trial design