Researchers at Johns Hopkins have shown that a drug commonly used to lower blood pressure reverses muscle wasting in genetically engineered mice with Marfan syndrome and also prevents muscle degeneration in mice with Duchenne muscular dystrophy. The results are reported online this week at Nature Medicine.
In 2006, a team led by Harry “Hal” Dietz, M.D., discovered that treating Marfan mice with losartan (Cozaar) dramatically strengthens the aorta, the major artery carrying blood away from the heart, and prevents enlargement and risk of bursting, a condition known as aortic aneurysm. A clinical trial to assess how effective losartan is for treating people with Marfan will launch within weeks.
“In addition to the aortic defect, children with severe Marfan syndrome often have very small, weak muscles, and adults with Marfan often can’t gain muscle mass despite adequate nutrition and exercise,” explains Dietz, a professor at the McKusick-Nathans Institute of Genetic Medicine at The Johns Hopkins University School of Medicine.
Dietz and his colleagues had previously discovered that many features of Marfan syndrome, including aortic aneurysm, arise from excess activity of TGF-beta, a protein that instructs cell behavior. Marfan mice have muscles containing much scar tissue between unusually small muscle fibers, which also show evidence of too much TGF-beta activity. Dietz’s team reasoned that blocking the activity of TGF-beta might restore normal muscle structure and function.
“We may have a real treatment alternative for a fatal disease-Duchenne muscular dystrophy-that improves both length and quality of life,” says Cohn.
“For so many reasons, we’re excited about these studies and their potential to transform the care of patients with both Marfan syndrome and Duchenne muscular dystrophy,” says Dietz. “First, this treatment strategy comes from understanding the basic science, the molecular underpinnings of the disease. Second, the treatment has worked exceptionally well in animal models. Third, we are not dealing with a mysterious compound that was simply pulled off the shelf – losartan has already been proven safe,” says Dietz.
“Furthermore, losing the ability to regenerate muscle over time is seen in many inherited and acquired muscle diseases and is even part of the normal aging process,” adds Cohn. “We may only be seeing the tip of the iceberg.”
Losartan, first approved for use as a blood pressure medication in 1995 by the U.S. Food and Drug Administration, often is used as an alternative to other antihypertensive drugs in people who cannot tolerate other blood pressure medicines.