Clinical trial of drug for Marfan’s Syndrome calls for volunteers

Children born with Marfan syndrome, a genetic disorder involving the connective tissue, have a variety of physical signs – disproportionately long arms, legs, fingers and toes; scoliosis or other spinal curvature; nearsightedness; unusually large lungs; and stretch marks on the skin. But one of the most dangerous effects of the disease is the development of an enlarged aorta, which can lead to rupture of the heart’s largest artery and to sudden death.

In patients with Marfan syndrome, the aorta, the large artery that carries blood away from the heart to the body, stretches and enlarges so much that it develops a tear, or dissection, that blocks blood flow or eventually bursts. About 90 percent of all patients with Marfan syndrome will need aortic surgery in their lifetime to repair the enlarged aorta, called an aortic aneurysm.

Researchers at Washington University School of Medicine in St. Louis are seeking volunteers, ages 6 months to 25 years old, for a three-year clinical trial of a drug that has been shown to prevent the development of aortic aneurysm in mice. The drug, losartan (brand name Cozaar), lowers the activity of the protein transforming growth factor beta (TGFß), which researchers have found to be the likely culprit in the physical effects of Marfan syndrome.

Losartan is commonly prescribed for high blood pressure and has been shown to be safe for children and adults with few side effects, said Angela Sharkey, M.D., co-principal investigator of the trial at the School of Medicine and director of the Marfan Syndrome Clinic at St. Louis Children’s Hospital.

“Losartan works to alter the extracellular matrix or support structure for the aorta,” said Sharkey, associate professor of pediatrics. “In studies performed in the laboratory of Dr. Hal Dietz at Johns Hopkins School of Medicine, losartan was given to mice with Marfan syndrome, and in these animals, the size of their aortas actually normalize.”

Marfan syndrome affects about 1 in 5,000 individuals. Most patients with Marfan syndrome are given beta blockers to lower blood pressure and stress on the aorta. Before the use of beta blockers, patients had a life expectancy of 45 years. Since beta blockers and elective surgical repair of aortic aneurysms have become the standard of care, patients have a life expectancy of 70 years.

While beta blockers can slow the growth of an aortic aneurysm, they only delay eventual surgery. Sharkey said the trial seeks to determine if losartan will eliminate the need for surgery in patients with Marfan syndrome.

“We know that a beta blocker will delay surgery, but if we can find a means to prevent surgery, that would be the greatest scenario,” she said. “The potential benefits to the body are profound.”

In the randomized trial, half of patients will receive a beta blocker drug and half will receive losartan. Patients must have no history of asthma or previous aortic surgery and have no other genetic syndrome other than Marfan syndrome. Children will be seen at the Marfan Syndrome Clinic at St. Louis Children’s Hospital, headed by Sharkey. Adults with the disorder will be seen at the Barnes-Jewish Hospital Marfan Clinic, headed by Alan Braverman, M.D., co-principal investigator of the School of Medicine study and professor of medicine at the School of Medicine.

The trial is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health and the National Marfan Foundation.

For more information about the trial or how to participate, call Cheryl Rainey, study coordinator, at (314) 454-6095, or visit

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.