Medical Genetics in Ophthalmology: Through the Lens of Genetics-Informed Therapies OnDemand-Gene-Agnostic Therapies for Inherited Retinal Degenerations

Gene-Agnostic Therapies for Inherited Retinal Degenerations

Video Transcription

Video Summary

Dr. Peter Cappuccino discussed gene-agnostic therapies for inherited retinal diseases (IRDs), focusing on Stargardt's disease (ABCA4 retinopathy) and retinitis pigmentosa (RP). He explained that rather than correcting genetic mutations, these therapies target the cellular damage caused by them. In Stargardt's disease, ABCA4 dysfunction leads to toxic accumulation of A2E, causing retinal cell death. Treatments include Tinlarabin, an oral inhibitor of retinol binding protein 4, which slowed macular atrophy in clinical trials, and metformin, which reduces A2E accumulation and is being tested for efficacy. Gene therapy delivering BRORA showed promise in early trials. For RP, oxidative stress contributes to photoreceptor death after rod loss. Antioxidants like N-acetylcysteine (NAC) showed safety and modest vision improvements in early trials, and a large, ongoing Phase 3 trial aims to assess long-term benefits. These approaches complement gene-specific therapies and could broadly benefit patients with diverse genetic causes of IRDs.

Asset Subtitle

Peter Campochiaro, MD

Keywords

gene-agnostic therapies

inherited retinal diseases

Stargardt's disease

retinitis pigmentosa

oxidative stress