Mimicking the Massively Muscular

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While it's not yet clear if similar rates will be seen in humans, high doses of anabolic steroids, which carry serious side effects, increase muscle mass by a maximum of 15 to 20 percent. And because myostatin is found only in muscle, knocking it out does not appear to have the adverse effects of broader-acting steroids.

Acceleron plans to begin trials of its drug for muscular dystrophy, a genetic disorder of progressive muscle loss that usually kills sufferers before they reach age 30, in early 2008. Trials for cancer and ALS will follow.

Acceleron's Big Pharma competitors are farther along. In 2005, Wyeth, headquartered in Madison, NJ, began a clinical trial of an antibody to myostatin that binds to it and blocks its activity, as a treatment for two forms of muscular dystrophy. Results were expected to be released late last year, but the company declined to comment on the current status. Amgen, headquartered in Thousand Oaks, CA, is analyzing results from a recently completed safety trial of its own myostatin inhibitor. The company is also testing a second inhibitor as a countermeasure to space-flight-induced muscle changes. Mice aboard the Space Shuttle Endeavor in August were given Amgen's experimental drug to determine if it could slow muscle loss in microgravity.

While initial clinical trials are focused on relatively rare conditions such as muscular dystrophy, safe muscle-building drugs have a broad potential market. "There is no effective agent to prevent the accelerated loss of muscle associated with disease, infection, or illness, such as cancer, heart failure, and kidney disease and dialysis," says William Evans, director of the Nutrition, Metabolism, and Exercise Laboratory at the University of Arkansas for Medical Sciences. Muscle loss is linked to increased mortality in these patients, as well as to an individual's level of disability resulting from normal aging. "As treatments of disease like cancer and heart failure become more effective, the issue becomes more prominent," says Evans. For example, treating cancer patients with a muscle-building drug may allow oncologists to administer extra rounds of chemotherapy.

In addition to treating muscle wasting, such drugs might prove effective in treating metabolic disorders, such as insulin resistance, which is linked to obesity and diabetes. Previous research has shown that diet-induced obese mice given Acceleron's drug showed an increase in lean muscle mass and reduced fasting glucose and insulin levels. Says Evans, "I think these drugs, perhaps used in combo with exercise, might have great potential in reversing the trend toward increasing obesity and decreasing muscle mass."