The Ghent Marfan Trial — A randomized, double-blind placebo controlled trial with losartan in Marfan patients treated with β-blockers

Genetic Dissection of Marfan Syndrome and Related Connective Tissue Disorders: An Update 2012

“…Mouse models suggested that administration of the angiotensin II type 1 receptor (AT1) blocker losartan could downregulate TGF ␤ signalling, prevent aneurysm formation and even partially reverse manifestations of MFS in fibrillin-deficient mice [Habashi et al, 2006]. Several clinical trials to evaluate the efficacy of losartan therapy in MFS patients are currently under way [Gambarin et al, 2009;Detaint et al, 2010;Radonic et al, 2010;Möberg et al, 2011], and there is legitimate hope that this therapy may reduce the risk for aneurysm formation in MFS-and perhaps LDSpatients in the future. Furthermore, noncanonical (Smadindependent) TGF ␤ signalling has also been shown to promote aortic disease in MFS mice, opening additional potential therapeutic strategies [Holm et al, 2011].…”

A healthy tension in translational research

“…Three additional clinical trials of losartan in children and adults with MFS have now reported similar protection (23)(24)(25). While the results of additional randomized trials that are underway will be required to fully elucidate therapeutic potential and refine therapeutic protocols (26)(27)(28)(29), this experience heralds true progress in the decades-long effort to inform the treatment of MFS and related disorders through basic science inquiry.…”

Marfan Syndrome

“…The University of Ghent trial [ 88 ] has a design similar to the French trial, but also evaluates the evolution of aortic stiffness over time. The objective is to include 174 MFS patients (age ≥ 10 years and z-score ≥ 2).…”