THALIDOMIDE IS AN INHIBITOR OF ANGIOGENESIS

Thalidomide is a potent teratogen causing dysmelia (stunted limb growt h) in humans. We have demonstrated that orally administered thalidomid e is an inhibitor of angiogenesis induced by basic fibroblast growth f actor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activ ity correlated with the teratogenicity but not with the sedative or th e mild immunosuppressive properties of thalidomide. Electron microscop ic examination of the corneal neovascularization of thalidomide-treate d rabbits revealed specific ultrastructural changes similar to those s een in the deformed limb bud vasculature of thalidomide-treated embryo s. These experiments shed light on the mechanism of thalidomide's tera togenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases d ependent on angiogenesis.