NEW YORK (Reuters Health) - It sounds like just a couch potato's dream, but new research may have brought exercise-in-a-pill a step closer to reality.

In experiments with mice, scientists identified a protein enzyme that, when overactive, mimics the effects of aerobic exercise on skeletal muscle. They say the finding now points to targets for drug development that could help people with medical conditions that exercise could benefit, but that make physical activity difficult.

The discovery that a single enzyme triggers such effects on muscle was "kind of a shock," the study's lead author, Dr. Hai Wu, told Reuters Health.

His team found that muscle in mice engineered to have an overactive form of the enzyme--called calmodulin-dependent protein kinase, or CaMK--easily transformed from so-called fast-twitch muscle fibers, which tire easily, to fatigue-resistant slow-twitch muscle fibers.

Slow-twitch muscle fibers specialize in endurance. Marathon runners, for example, have lots of these fibers, said Wu, a researcher at the University of Texas Southwestern Medical Center in Dallas.

He and his colleagues found that CaMK benefits muscle by triggering a signaling pathway that increases the number of mitochondria in muscle cells. Mitochondria are essential in providing energy to cells. Endurance exercise can also increase mitochondria in muscle cells, but only with long-term, regular activity, Wu said.

According to Wu and his colleagues, who report their findings in the April 12th issue of Science, all of this raises the possibility of developing a drug that essentially mimics the effects of endurance exercise on skeletal muscle.

The intention, however, is not to provide an exercise pill to the unmotivated. Wu said the hope is to come up with a treatment for patients with activity-limiting diseases like congestive heart failure, for whom exercise could improve their endurance and quality of life.

But such a drug, he noted, is likely "decades" away.

SOURCE: Science 2002;296:349-352.

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