Project 4 - Development of a one-time gene therapy for age-related macular degeneration

Neovascular age-related macular degeneration (wet AMD) is a multifactorial disease leading to loss of central vision. It is the leading cause for blindness in the elderly western population and poses a significant clinical and economic burden. Implementation of anti-VEGF drugs like aflibercept, bevacizumab, ranibizumab and more recently brolucizumab in clinical practice has dramatically improved the prognosis of wet AMD.

However, currently there is no cure for wet AMD and available treatments cannot prevent the development of atrophy and scar formation. Thus, it is mandatory to find new treatment options to address the unmet medical need in this devastating sight threatening disease. In this project, we propose the development of a one-time gene therapy treatment of AMD based on a novel therapeutic target. Different from previous approaches that directly inhibit the growth factor VEGFA, our approach targets both proangiogenic and proinflammatory signaling pathways crucially involved in the pathogenesis of AMD-related vision loss.

Own preliminary results suggest that inhibition of the novel target reduces the formation of leaky choroidal blood vessels and the extent of lesion formation in the laser-induced choroidal neovascularization (CNV) mouse model of wet AMD. Our overarching goal is to provide preclinical proof of concept for a novel, one-time gene therapy approach against wet AMD and to select an optimal candidate for future clinical translation.