The drug losartan may prevent lethal damage to the aorta in people with a genetic disorder called Marfan syndrome, a preliminary study shows. The findings have already paved the way for a large-scale trial of the drug for this condition.

“If this observational information is backed up and confirmed by the randomized clinical trial … it would be a tremendous breakthrough in the management of Marfan’s syndrome,” says Alan Braverman, a cardiologist at the Washington University in St. Louis, who wasn’t involved in this study.

People with Marfan syndrome — a genetic condition that can be inherited or, in roughly one-fourth of cases, can appear out of nowhere — tend to have long limbs and fingers, are often tall and may encounter a broad range of symptoms. The worst complication is ballooning of the aorta, the huge artery that carries blood out of the heart. This weakens the vessel over time and poses a risk of lethal rupture that can be prevented only with major surgery. Aorta injury is the most common cause of death from Marfan syndrome.

In the 1990s, cardiologist Harry Dietz of Johns Hopkins University in Baltimore led a team of researchers that discovered that Marfan syndrome stems from a mutation in the FBN1 gene that encodes a glycoprotein called fibrillin-1.In people with the syndrome, a lack of fibrillin-1 allows excess production of a signaling protein called transforming growth factor beta, which kicks on a host of reactions that damage the aorta walls over time, says research physician Benjamin Brooke of Johns Hopkins.

Further research suggested that losartan slashes circulating levels of transforming growth factor beta, interrupting this cycle of aorta damage. The drug also eases blood pressure, which puts less strain on the aorta itself, studies in mice showed.

All this suggested that the drug, already approved for high blood pressure, might help Marfan syndrome patients. From 2003 to 2006, Dietz, Brooke and their colleagues identified 18 children with Marfan syndrome, ranging in age from 14 months to 16 years. All had severe disease, including steadily widening aortas in the slow process of forming aneurysms, or bulges, in the worst possible place — near the heart.

The scientists assigned all but one to receive the oral drug losartan, which is marketed as Cozaar by Merck and Co. The other patient got a similar drug called irbesartan, sold as Avapro by Bristol-Myers-Squibb.

The researchers report in the June 26 New England Journal of Medicine that, in every single patient, enlargement of the aorta slowed. The average reduction among the patients was statistically significant. Growth in the diameter of the vessel fell from a yearly average of 3.5 millimeters to less than 0.5 millimeters after two years, echocardiogram readings showed.

When the results were adjusted for normal growth of the vessel in accordance with the ages and sizes of the children, the aortas actually slowed to a growth pace that allowed other tissue growth to catch up, Brooke says.

Marfan syndrome patients often receive medications known as beta blockers or other heart drugs to ease the strain on the aorta. As a control group in this study, the researchers monitored 65 other Marfan syndrome patients, average age 12, who received beta blockers. Aorta diameters in this group grew more rapidly than in those treated with losartan.

Marfan research has taken a classic route from genetic discovery to laboratory and animal tests and now to promising findings in severely threatened patients, says physician Reed Pyeritz of the University of Pennsylvania in Philadelphia, writing in an editorial in the same NEJM issue. If these preliminary findings are replicated, he says,“the treatment of Marfan syndrome will go down in history as an early triumph of translational medicine

Dietz, Brooke and others are currently recruiting people with Marfan syndrome as part of a larger clinical trial getting under way. Their goal is 600 participants under age 24. The trial will compare aorta aneurysms in people randomly assigned to receive losartan or beta blockers.

It’s important to complete a large trial before jumping to the conclusion that the drug works, Brooke says. The National Marfan Foundation agrees. “We have urged our members to consider participating in the clinical trial,” the organization announced this week.

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