May 13, 2008

Viagra Shows Promise for Heart Problems In DMD, BMD

Treatment with sildenafil (Viagra) significantly improved heart function in mice with a disease resembling Duchenne muscular dystrophy (DMD) due to the absence of the protein dystrophin, suggesting a possible new approach to treating cardiac deterioration in humans with the disease.

A research team coordinated by Christine Des Rosiers at the University of Montreal and including MDA grantee Basil Petrof at McGill University in Montreal announced its findings today in Proceedings of the National Academy of Sciences.

The idea of treating dystrophin-deficient mice with sildenafil was based on previous studies suggesting that the hearts of these mice are more susceptible than normal hearts to stress-induced cell death because of a deficiency of a compound called cyclic guanosine monophosphate, or cGMP.

Sildenafil and related medications, which have U.S. Food and Drug Administration approval to treat erectile dysfunction, increase cGMP by blocking the enzyme that normally breaks it down. Increased levels of cGMP result in dilation of blood vessels, including the coronary arteries.

DMD-affected mice treated with sildenafil had 44 percent less damage to heart-muscle cells than did untreated mice when their hearts were stressed with a drug known to increase cardiac workload.

Boys and young men with DMD and the related Becker muscular dystrophy (BMD) lack dystrophin in their hearts and skeletal muscles, leading to progressive weakness and loss of cardiac and respiratory muscle function. Dystrophin has structural and biochemical signaling functions in muscle.

In DMD, dystrophin is completely absent, while in BMD, a less severe condition, functional dystrophin is present but deficient. Heart-muscle deterioration, or cardiomyopathy, is a leading cause of death in both MDs.

The researchers say their findings demonstrate that enhancing signaling by cGMP in dystrophin-deficient hearts improves cardiac contraction and energy production and helps the membranes surrounding cardiac muscle cells resist tearing under stress.

They note that treatment with sildenafil and similar medications, which already exist, “constitutes a potential clinical avenue for treatment of the dystrophin-related cardiomyopathies.”