Viagra improved heart
function in DMD mice

Arecent study has found treatment with sildenafil (Viagra) significantly improved heart function in mice missing the protein dystrophin and showing a disease resembling

Duchenne muscular dystrophy (DMD). Heart-muscle deterioration (cardiomyopathy) is a leading cause of death in boys and men with DMD and the closely related Becker muscular dystrophy (BMD).

A research team coordinated by Christine Des Rosiers at the University of Montreal, which included MDA grantee Basil Petrof at McGill University in Montreal, announced its findings May 13 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, as well as pulmonary hypertension, increase cGMP by blocking the enzyme that normally breaks it down. Increased levels of cGMP result in dilation of

blood vessels, including the coron ary 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.

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 car-diomyopathies.” However, currently there is no clinical data to support the use of these drugs in people.

Utrophin-stimulating
compound improves
strength, endurance
in mice

An experimental compound that stimulates production of the muscle protein utrophin increased strength in dystrophin-deficient mice with a disease resembling Duchenne muscular dystrophy (DMD).

The compound, called SMT

C1100, is made

by Summit Corp. of Oxford, United Kingdom. When combined with a corticosteroid (prednisone-like medication), it reduced muscle fatigue during exercise.

The findings were first presented at the New Directions

Christine Des Rosiers and colleagues found the hearts of DMD mice treated _{with Viagra showed much less damage than those of untreated mice, while in Muscle} Summit Corp. researchers found the utrophin-stimulating compound C1100 ^{Biology and} increased strength in DMD mice. Diseases con-

ference held in New

Orleans April

27-30. The company says it plans to begin phase 1 clinical trials in 2009.

SMT C1100 is a small molecule designed to increase production of utrophin, a protein that at least partially compensates for the lack of functional dystrophin that characterizes DMD and Becker muscular dystrophy (BMD).

The major advantages of the utrophin-stimulating drug over some of the other strategies being developed for DMD and BMD are that the drug is oral; it has the potential to be effective in a wide range of patients; and, since people with DMD and BMD already make normal utrophin, it’s highly unlikely to cause an unwanted immune response.

Myotilin protein may be a
viable therapeutic target
in LGMD1A

Findings in a study published in the May issue of Muscle & Nerve show overproduction of the protein myotilin worsens the symptoms of type 1A limb-girdle muscular dystrophy (LGMD1A) in mice.

The myotilin gene, located on chromosome 5, carries instructions for the large myotilin protein found in the Z disc — the structure that anchors the thick and thin filaments that slide together to cause muscle to contract. Defects (mutations) in the myotilin gene lead to the production of abnormal (mutated) myotilin protein, which causes disorganization in the muscle fibers and is the underlying cause of LGMD1A.

MDA grantee Michael Hauser at the Center for Human Genetics at