How Doctors Help The Dopers

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The key, then, to using IGF-1 safely and effectively in muscular-dystrophy patients lies in getting enough of the hormone directly to the muscle. So Sweeney's group is perfecting a version of gene therapy, the most efficient way to dump a large amount of genetic material into a tissue as extensive as muscle (about 40% of body weight comes from muscle). He packs the IGF-1 gene into a harmless cold virus and injects the entire package directly into muscle. Once the IGF-1 gene inserts itself into the genome of the muscle cell, it begins to churn out the insulin-like growth factor that activates muscle expansion. Muscles in mice injected this way grew up to 30% larger than in normal animals, even when the mice didn't exercise. And as the animals aged, their muscles remained strong, as vigorous as if they belonged to far younger mice. In the coming months, Sweeney plans to inject IGF-1 into dogs to learn more about how the added growth factor would operate in a larger, mammalian body that more closely resembles that of humans.

Boosting IGF-1 levels is only half the story. Sweeney is also trying to tip the balance by shutting down myostatin, a compound that inhibits IGF-1 activity in the muscle. The pharmaceutical maker Wyeth Ayerst is testing a myostatin blocker in early trials of healthy humans, and hopes that it may become a new treatment option for those with muscular dystrophy or for the elderly who have become frail from the normal muscle wasting that occurs with aging.

Other labs are taking a different approach, focusing on enhancing the supply of oxygen that fuels everything the muscle cells do. And here too, athletes are eagerly dogging the footsteps of medical researchers, specifically those working to treat chronic anemias, conditions in which red blood cells dwindle to dangerously low levels, starving tissues of oxygen. In athletes, prolonged exertion leads to oxygen depletion in the muscles, which causes fatigue.

When researchers found a way to bioengineer a version of the human hormone erythropoeitin (EPO), which acts as the body's trigger to create more red blood cells, it didn't take long for athletes with perfectly normal red-blood-cell counts to exploit the technology. French cyclists were caught using EPO in the 1998 Tour de France; Olympic officials began testing athletes at the Sydney Games in 2000.

EPO may shunt more oxygen to the muscles, but it comes at a price. "If you take too much EPO," explains WADA's Dr. Gary Wadler, professor of clinical medicine at New York University, "the production of red blood cells is excessive, and the blood becomes viscous — it's like sludge." In the late 1980s, when EPO became available, nearly 20 European cyclists died of causes that some experts suspect were linked to EPO.

Some athletes are banking on a different strategy: gene therapy. Researchers have developed techniques to insert EPO-producing genes into cells so they can generate additional amounts of EPO long term. But again, says Wadler, "since overproduction of red cells is potentially lethal, this technique requires a pharmacological on-off switch." Researchers are using various techniques to devise controllable EPO delivery systems, in which genes inserted into the skin can be turned on and off either by taking a pill or rubbing a chemical on the skin. Other scientific groups are encapsulating genetically engineered EPO-producing cells in man-made biological carriers and implanting these microbioreactors into tissue, where they deliver a controlled low-dose supply of the hormone.