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Common blood pressure drug treats muscular dystrophy in mice

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.

First, the research team injected Marfan mice with a protein that binds TGF-beta and renders it inactive. This TGF-beta-blocking protein caused muscle fibers in these mice to grow bigger than those in untreated Marfan mice. "Not only did the muscles look bigger and better under the microscope," says Dietz, "the mice were also stronger and showed reduced fatigue."

The team then treated Marfan mice with losartan, a medication known to be safe in
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
21-Jan-2007


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