Gene therapy for age-related macular degeneration

Abstract

Presentation Description : Age-related macular degeneration (AMD) is an increasing burden of vision loss in people who might otherwise remain healthy and active in later life. The alternate complement pathway has been identified as having a key role in AMD disease pathogenesis. In a recent study of 468 patients with the geographic atrophy form of AMD, 20% had low serum complement factor I (CFI) and amongst these, 25% had CFI gene variants. Hence supporting a monogenic cause in 4% of AMD patients with geographic atrophy overall. Previous work in our laboratory in conjunction with Gyroscope Therapeutics (since acquired by Novartis) led to the development of an adeno-associated viral (AAV) vector encoding secretable CFI. This resulted in a multicentre retinal gene therapy clinical trial sponsored by Novartis but which has since been terminated. In this talk I will provide an overview of the rationale behind targeting the complement system using AAV gene therapy in the treatment of AMD. I will also discuss gene therapy in the context of hypomorphic mutations in the cadherin gene, CDHR1, which present with a very similar phenotype to geographic atrophy and might often be missed due to the silent nature of the gene mutation which affects splicing.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.