Background: Age-related macular degeneration (AMD) is the leading cause of blindness in elderly patients, affecting more than 8 million individuals in the US alone. Currently, there is no effective therapy for 90% of AMD patients with “dry” or atrophic form of AMD. The retinal pigment epithelial (RPE) cells are vital for proper functioning neurosensory retina. Age-related changes in RPE cells are a hallmark of early AMD and contribute to pathology and visual morbidity associated with advanced AMD.

Invention: Using a HTS assay, we identified a small molecule 424 as the lead compound with IC50=~20nM. It is non-toxic in vitro and significantly improves RPE viability in the tert-butyl hydroperoxide (TBHP) challenge assay, which induces oxidative stress (Figure 1).

• Tolerability and pharmacokinetic studies for topical (eye drops) and intravitreal delivery of compound 424 are underway.
• We have identified additional, novel chemotypes that are under development.

IP status: PRV application filed.

Innovators: Mark Fields, Ph.D., Lucian Del Priore, M.D., Ph.D