Editors' ChoicePhysiology

Therapy for Marfan Syndrome

Science's STKE  11 Apr 2006:
Vol. 2006, Issue 330, pp. tw125
DOI: 10.1126/stke.3302006tw125

Marfan syndrome (MFS) is a hereditary disorder characterized by systemwide defects in connective tissue. People with MFS have a greatly increased risk of developing an aortic aneurysm, a bulge in the wall of the aorta that can rupture and cause life-threatening internal bleeding. Studying a mouse model of MFS, Habashi et al. found that aneurysm formation is accompanied by activation of the transforming growth factor-β (TGF-β) signaling pathway in the aortic wall. Treatment of the MFS mice with losartan, a drug recently shown to antagonize TGF-β signaling in other disease states, almost completely normalized the aortic phenotype in the MFS mice, even after an aneurysm had formed. Losartan is already widely used to control high blood pressure, and the authors suggest that a prospective clinical trial in MFS patients is warranted.

J. P. Habashi, D. P. Judge, T. M. Holm, R. D. Cohn, B. L. Loeys, T. K. Cooper, L. Myers, E. C. Klein, G. Liu, C. Calvi, M. Podowski, E. R. Neptune, M. K. Halushka, D. Bedja, K. Gabrielson, D. B. Rifkin, L. Carta, F. Ramirez, D. L. Huso, H. C. Dietz, Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312, 117-121 (2006). [Abstract] [Full Text]