Sterculic Acid Analogs to Inhibit Macular Degeneration

ABSTRACT The long-term product goal of this project is a small molecule therapeutic for choroidal neovascularization (CNV, the hallmark of wet age-related macular degradation), an abnormal growth of blood vessels in the choroid layer of the eye that results in damage to the retina and consequent blindness. Our lead compound is the natural product sterculic acid, which has been shown to inhibit CNV in animal models. The main current treatment options for CNV involves intravitreal injection of anti-VEGF agents such as ranibizumab (Lucentis), aflibercept (Eylea) and (in off-label use) bevacizumab (Avastin) which, while often slowing disease progression, have a number of side-effects associated with the method of administration. A small molecule therapeutic which might be administered topically would present obvious advantages. Sterculic acid has very recently been shown to mitigate the induction of CNV in a rat model and to antagonize the inflammatory effects of 7- ketocholesterol (7KCh) in cultured human re