Blood pressure medication may revolutionize treatment of Marfan syndrome

A commonly prescribed blood pressure medication may provide the first ray of hope in preventing potentially deadly complications of Marfan syndrome, a genetic disease that weakens the structural meshwork of blood vessels. People who have Marfan syndrome have a high risk of developing aortic aneurysm, which can lead to rupture of the heart's largest artery, causing sudden death.

In studies published in the April 7, 2006, issue of the journal Science, Howard Hughes Medical Institute researchers at Johns Hopkins University School of Medicine have shown in mice that the drug losartan, which is manufactured by Merck and sold under the brand name Cozaar, can prevent progression of Marfan syndrome and may also restore normal architecture to the wall of the aorta.

Marfan syndrome is a connective tissue disorder that affects about one in 5,000 individuals. Manifestations include long bone overgrowth, lens dislocation, emphysema, thickening and dysfunction of the heart's mitral valve, and aortic aneurysm with a predisposition for early vascular rupture and sudden death.

Losartan attenuates development of aortic aneurysm by lowering the activity of a pervasive developmental molecule called transforming growth factor beta. In a sea change in thinking about the origins of the disease, researchers have recently discovered that transforming growth factor beta -- not simply a defect in a structural protein -- is most likely responsible for the syndrome's catastrophic developmental defects.

"This is the first therapy for Marfan syndrome that was borne of a systematic effort to elucidate the pathogenesis of the disease," said the senior author of the study, Harry C. Dietz, a Howard Hughes Medical Institute investigator at Johns Hopkins. "I think that this is a rare example where things lived up to the promise that was expressed upon launching the Human Genome Project: If we can identify the genes responsible for a disease, then we will uncover unantici

Contact: Jim Keeley
Howard Hughes Medical Institute

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