Grant: Project Grant

Age-related Macular Degeneration (AMD) is the leading cause of adult vision loss. AMD exists in 'wet' and 'dry' clinical forms. The 'wet' form of AMD is characterized by increased, erratic and destructive growth of blood vessels from the choroid, a vascular layer of the outer wall of the eye, into the retina. The early phase of the 'dry' form is characterized by thickening of membranes in the choroid. The compromised choroid integrity is accompanied by a recruitment of white blood cells called macrophages followed by loss of photoreceptors (light detecting cells). Several treatments are available for 'wet' AMD; a single molecule has recently been approved for 'dry' AMD, albeit with modest visual improvement, yet provides investor encouragement on the horizon for AMD treatment. Overall, 'dry' AMD remains an unmet clinical need. Compelling evidence points to a major role for innate inflammation and pro-inflammatory pathways in the genesis and progression of AMD. Although previous focus on certain components of inflammation have yielded modest benefits in disease development and progression, other inflammatory pathways seem more promising. In this regard, we have discovered a new drug candidate with pronounced efficacy in various models of inflammation, and particularly in ischemic and degenerative retinopathies. Aiming for approval of this promising drug candidate by regulatory agencies, we plan pre-clinical studies to establish the dosage, to test efficacy once inflammation is triggered (in line with clinical condition), to enhance formulation for prolonged duration of action, and to design backups with optimal properties to treat AMD, using biomolecular simulations in atomistic detail. Along with aligned commercial partners, this required program is bound to bring us closer to an "Investigational New Drug" designation for further development.