Improved Therapy for AMD

DESCRIPTION (provided by applicant): Improved therapy for AMD Age-related macular degeneration (AMD) is a leading cause of visual loss (http://www.nei.nih.gov/eyedata/pbd4.asp) affecting more than 1.75 million people in the USA. Vascular endothelial growth factor (VEGF) is a major driver of choroidal neovascularisation, a central process in the pathogenesis of wet AMD. FDA approval of inhibitors of VEGF has revolutionized therapy for this serious disease. However, such therapies require repeated, monthly injections and are associated with significant morbidity. We have developed an AAV-based inducible gene transfer system for local delivery of therapeutic antibodies (Fang, 2006, 2007). Preliminary work demonstrates tightly regulated, long-term (gt1 yr.), high level expression (gt1 mg/ml) of an antibody suitable for therapy of AMD. The overall goal of the present application is to utilize our rapamycin-regulated AAV system to deliver an anti-VEGF antibody into the eye. This novel therapeutic approach is expected to eliminate monthly injections, reduce neovascularization and curtail side effects (e.g. endophthalmitis) of present therapies. PUBLIC HEALTH RELEVANCE: Improved therapy for AMD Age-related macular degeneration (AMD) is a leading cause of visual loss (http://www.nei.nih.gov/eyedata/pbd4.asp) affecting more than 1.75 million people in the USA. FDA approval of inhibitors of vascular endothelial growth factor (VEGF) has revolutionized therapy for this serious disease. However, such therapies require repeated, monthly injections that can have serious side effects. We have developed an improved therapy that will require only one treatment.