Towards a gene therapy for age-related macular degeneration (AMD)

Introduction

While the blood neural barriers represent significant hurdles for the development of gene therapies for neurological and ophthalmological conditions, it is now becoming clear that many of these conditions actually present with disrupted barrier integrity as the driving force of the pathology.

Background

Included in these diseases is age-related macular degeneration (AMD), in which we have shown that the blood-retina barrier (BRB) is sub-clinically disrupted and is a key driving force for disease progression (ERC funded Retina Rhythm project).

Need for Novel Therapy

Specifically related to this Proof of Concept grant, a novel form of therapy for the end stage of AMD, namely geographic atrophy (GA), is now desperately needed. A targeted approach to locally delivering adeno-associated virus (AAV) to endothelial cells of the BRB would offer the opportunity to restore barrier function and prevent disease.

Current Limitations

However, the current tools available to achieve this localized approach to gene therapy are not optimum.

Proposed Solution

Here we will use an exosome encapsulated and endothelial cell-specific AAV to achieve robust transduction of retinal endothelial cells. This modified and optimized AAV (Opti-AAV) will represent a novel tool in translating recently identified biological mechanisms into real and meaningful therapies for patients.