"GW501516" - Reduces fat & greatly produces slow twitch muscle
Mice which can run almost twice the distance of normal mice have been genetically engineered by US scientists.
"This is the first animal engineered for increased endurance," says Ronald Evans of the Salk Institute in La Jolla, California, whose team created the mice.
But Evans adds that the work also suggests that drugs already in clinical development may, unintentionally, boost endurance. "The potential for this to be abused by athletes is real," he points out.
Pills that mimic the benefit of exercise could also help patients whose conditions prevent them from exercising and building muscle, such as people suffering from obesity. In fact, it was while studying genes involved in obesity and fat metabolism that Evans's team stumbled across how to make mice long distance runners.
The focus of their work was a protein called PPARdelta, known to play a role in promoting the burning of fat and fighting obesity.
In previous work, his team has shown that increasing the activity of PPARdelta in fat cells encourages cells to reduce their fat stores. In the body, however, the greatest consumer of fat is slow twitch muscle, the type of muscle that gives athletes endurance. The other major type of muscle is fast twitch which is powered mainly by sugar and is responsible for strength and rapid reaction.
Conditioned athletes
So Evans's team genetically-engineered mice to produce extra PPARdelta in their muscle. As expected, when these engineered mice and control mice were put on a high fat diet for 97 days, the engineered mice experience only one-third of the weight gain that controls did.
But to the researchers' surprise, increasing PPARdelta also had a dramatic effect on the muscle composition itself: it doubled the amount of slow twitch muscle.
"These mice are genetically in better shape. They behave like conditioned athletes," says Evans. When tested, the marathon mice were able to run 92 per cent longer than normal controls.
It is unclear whether boosting PPARdelta levels later in life - or in people - would similarly enhance endurance. But, by coincidence, a drug called GW501516 which activates PPARdelta directly - is being clinically tested as a treatment to lower blood cholesterol and fat by the pharmaceutical company GlaxoSmithKline.
Evans has already shown the new drug causes many of the same genetic changes in muscle cells triggered by increasing levels of PPARdelta protein.
Therapeutic purposes
The question that remains is whether the drug alone will be enough to increase endurance "I suspect that animals training with the drug will increase endurance more rapidly," predicts Evans.
Evans says he has no affiliation with GlaxoSmithKline. And the company has so far been able to provide any comment on the work.
Farnaz Khadem, a spokesperson for the World Anti-Doping Agency, which strives to make sporting competitions drug-free, says she would not be surprised if cheating athletes would try taking GW501516, if it becomes available.
"Most doping involves a substance developed for therapeutic purposes being used for a sports purpose," she says. "Medical science is moving forward, which is good. But it also means we've got to be on our toes."
"This is the first animal engineered for increased endurance," says Ronald Evans of the Salk Institute in La Jolla, California, whose team created the mice.
But Evans adds that the work also suggests that drugs already in clinical development may, unintentionally, boost endurance. "The potential for this to be abused by athletes is real," he points out.
Pills that mimic the benefit of exercise could also help patients whose conditions prevent them from exercising and building muscle, such as people suffering from obesity. In fact, it was while studying genes involved in obesity and fat metabolism that Evans's team stumbled across how to make mice long distance runners.
The focus of their work was a protein called PPARdelta, known to play a role in promoting the burning of fat and fighting obesity.
In previous work, his team has shown that increasing the activity of PPARdelta in fat cells encourages cells to reduce their fat stores. In the body, however, the greatest consumer of fat is slow twitch muscle, the type of muscle that gives athletes endurance. The other major type of muscle is fast twitch which is powered mainly by sugar and is responsible for strength and rapid reaction.
Conditioned athletes
So Evans's team genetically-engineered mice to produce extra PPARdelta in their muscle. As expected, when these engineered mice and control mice were put on a high fat diet for 97 days, the engineered mice experience only one-third of the weight gain that controls did.
But to the researchers' surprise, increasing PPARdelta also had a dramatic effect on the muscle composition itself: it doubled the amount of slow twitch muscle.
"These mice are genetically in better shape. They behave like conditioned athletes," says Evans. When tested, the marathon mice were able to run 92 per cent longer than normal controls.
It is unclear whether boosting PPARdelta levels later in life - or in people - would similarly enhance endurance. But, by coincidence, a drug called GW501516 which activates PPARdelta directly - is being clinically tested as a treatment to lower blood cholesterol and fat by the pharmaceutical company GlaxoSmithKline.
Evans has already shown the new drug causes many of the same genetic changes in muscle cells triggered by increasing levels of PPARdelta protein.
Therapeutic purposes
The question that remains is whether the drug alone will be enough to increase endurance "I suspect that animals training with the drug will increase endurance more rapidly," predicts Evans.
Evans says he has no affiliation with GlaxoSmithKline. And the company has so far been able to provide any comment on the work.
Farnaz Khadem, a spokesperson for the World Anti-Doping Agency, which strives to make sporting competitions drug-free, says she would not be surprised if cheating athletes would try taking GW501516, if it becomes available.
"Most doping involves a substance developed for therapeutic purposes being used for a sports purpose," she says. "Medical science is moving forward, which is good. But it also means we've got to be on our toes."
