Topical squalamine (Ohr Pharmaceutical), a small molecule being investigated for the treatment of neovascular age-related macular degeneration (nAMD) and other retinal vascular diseases, represents a novel therapy because of its mode of administration and multimodal mechanism of anti-angiogenic activity.
Glenn L. Stoller, MD, chief scientific officer, Ohr Pharmaceutical, New York, outlined the mechanism of action of squalamine. He explained that it is a calmodulin-binding molecule that acts within vascular endothelial cells.
The molecule enters the cells through cell membrane invaginations known as caveolae. Inside the cell, squalamine sequesters calmodulin away from its receptors and causes global suppression of calmodulin-dependent signaling that results in inhibition of VEGF- and basic fibroblast growth factor (bFGF)-mediated cell signaling, as well as decreased expression of cell surface integrins.