If results in humans are anything like they are in mice, it may be possible
to prevent life-threatening aortic aneurysms in patients with Marfan
syndrome by using an existing drug to strengthen aortic tissue. In
February, Children's Hospital Boston enrolled its first patient in a
multicenter, government-funded clinical trial to test this drug, called losartan.
People with Marfan syndrome, a genetic disorder affecting about 1 in 5,000 Americans, tend to be tall with long limbs and long faces. But the disease also weakens the aorta, often leading to aneurysms.
Beta blockers are sometimes used to lower blood pressure and reduce stress on the aorta, in hopes that this will prevent aneurysms from forming. But new evidence suggests that losartan may be far more protective. It
inhibits signaling by transforming growth factor-beta, a protein now
known to be overactive in Marfan syndrome, and blocks a cascade of
cellular events that weaken aortic tissue. In a landmark 2006 study,
losartan completely prevented aortic aneurysms in mice with Marfan
syndrome, and even reversed existing aortic damage.
The Phase III trial, co-led by Ron Lacro, MD, director of Children's Cardiovascular Genetics Clinic, aims to enroll about 600 patients aged 6 months to 25 years from about a dozen institutions. Patients will be
randomly assigned to receive losartan or the beta-blocker atenolol and
will be closely followed for three years.
"If we meet our recruitment goal, this would be the largest Marfan study ever done," Lacro says. "If losartan proves effective, it will have a huge
impact on management."
