Using a cell permeable peptide of caveolin, cavtratin, pre-clinical studies have demonstrated its ability to suppress multiple critical components of pathological angiogenesis and inhibit choroidal and retinal neovascularization. Additionally, the combined administration of cavtratin and anti-VEGF-A inhibited neovascularization more effectively than VEGF-A monotherapy suggesting a synergistic effect with the current standard of care therapy.
Our lead compound, CVX-51401, is a novel, optimized second generation caveolin modulator designed to have increased potency and efficacy both in vitro and in vivo.
Cavtratin reduces pathological retinal angiogenesis in an ischemic retinopathy model
CNV works synergistically with anti-VEGF
Sessa Lab - Yale University
Established in 1993, the Sessa Lab is run by William C. Sessa, PhD, Alfred Gilman Professor of Pharmacology and professor of medicine (cardiology). The Sessa labs research defined the molecular aspects and physiological implications of endothelial nitric oxide synthase (eNOS) activation and has contributed towards the elucidation of how nitric oxide regulates angiogenesis, vascular permeability and atherosclerosis. He made important contributions and revealed how extracellular cues such as growth factor (VEGF) stimulation or mechanical signals (blood flow) regulate intracellular signal transduction mechanisms including defining the role of protein lipidation, phosphorylation and protein-protein interactions paramount for endothelial cell homeostasis. Recently he has focused on how endothelial cells regulate LDL transport and fatty acid utilization to control vessel function normally and in cardiovascular pathologies. In the context of caveolin, current projects are examining the role of caveolin in lipid droplet formation and as a potential signaling scaffold independent of caveolae assembly. The team is also interested in developing potential therapeutics based on the caveolin scaffolding domain which has shown promise in a number of disease states.