Novel pharmacological strategies to prevent aortic complications in Marfan syndrome

The Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the FBN1 gene. Recent molecular studies, most performed in mouse models, revealed that the MFS is more a developmental abnormality with broad and complex effects on the morphogenesis and function of multiple organ systems. FBN1 haploinsufficiency and dysregulated transforming growth factor-beta (TGF-β) signaling seem to be critical for clinical manifestations in MFS including aortic root dilatation. Aortic root aneurysm and aortic dissection represent the main causes of morbidity and mortality in MFS. Most importantly, TGF-β antagonism through angiotensin II type 1 receptor blockers (ARBs), for example losartan, has been shown to prevent and possibly reverse aortic root dilatation in a mouse model of MFS. A first human study on a small pediatric cohort confirmed those promising results in reducing the aortic root growth over a follow-up period of 12 to 47 months. So, a large multicenter trial has been set up and results should be available soon. Other therapeutic strategies which might be combined with losartan include traditional β-blockade, doxycyclin and statins. Such management could offer the first potential for primary prevention of clinical manifestations in MFS.