2009 Astute Clinician Topic: Marfan syndrome and related disorders: from molecules to medicines
Our goal is to understand the genetic factors that predispose to aortic aneurysm, a condition accounting for 1–2 percent of deaths in industrialized countries. We have shown that the growth factor molecule TGF-beta drives many of the manifestations of Marfan syndrome, including aortic aneurysm, developmental emphysema, myxomatous valve changes and skeletal myopathy. Most importantly, these findings can be attenuated or prevented in validated animal models through TGF-beta antagonism in vivo. The identical mechanism and therapeutic response is relevant to other more common presentations of these important disease phenotypes. These data are illustrative of the promise that disease gene identification and elucidation of pathogenesis for rare Mendelian disorders will lead to the development of novel therapeutic strategies with broad application.