Exercise? Pop a pill

November 21, 2008

Athletics and drugs have sadly often gone hand in hand, and now a new research breakthrough which is intended to help people who cannot exercise much or at all, due to incapacity or illness, could be high on the list for cheating athletes.

Steroids boost muscle power so are misused by those needing strength in their events, but so far a drug that can build the endurance needed to run a marathon or take part in the Tour de France has not been available. Now, it could be. We have two types of muscle that move our body: bulky, fast-twitch muscles for power and speed, and slender slow-twitch muscles for endurance. Fast-twitch muscles burn sugar that must be stored in the muscle itself, while slow-twitch muscle burns fat.

A new study on mice at the Salk Institute in La Jolla, California suggests that there is a drug that can trick the body into “believing” it has exercised. A drug that has been developed for the treatment of metabolic disease, when taken in combination with exercise, gives mice the ability to run farther than exercise alone can and a separate chemical gave them greater endurance, even without the exercise.

Earlier studies had found that a red wine ingredient called resveratrol could build endurance, but only at enormous doses and by uncertain means. The natural route’s success, however limited, as usual set up a search for a pharmaceutical substitute. The chemicals tested in the new study are thought to work by specifically tapping into the molecular mechanisms that normally re-programme our muscle genes in response to exercise.

Of course it might not work on people, but the research team had previously found they could genetically engineer mice to produce more of the fat-burning slow-twitch muscle fibres, giving them nearly twice the running endurance of untrained adults. The key was boosting the activity of a gene in muscle called PPARd, known to control other genes important to muscle metabolism.

The researchers gave mice an experimental drug, known only as GW1516, that increases PPARd activity and is currently being tested for the treatment of metabolic disease in humans. However, the drug had no effect on the muscles and so they tried giving it to mice who were undergoing exercise training. I have a cute but entirely unfounded vision of a Stuart Little character with mini barbells in satin running shorts – or is that just me? The same dose and duration of GW1516 that had previously failed to alter performance, when paired with four weeks of exercise training, increased the animals’ running time by 68% and their running distance by 70%. The muscles of those mice also showed a unique “endurance gene signature,” including patterns of gene activity not seen with either the drug or exercise alone, according to the investigators. They then decided to try one more thing: a chemical known as AICAR that was known to act on a protein in the body called AMPK. The results are impressive, even in sedentary mice, four weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%.

When developed and trialled fully, this has therapeutic potential in treating certain muscle diseases such as wasting and frailty as well as cases of obesity where exercise is known to be beneficial but not physically possible. We also appear to be training mice for the 2012 Olympics, or at least increasing their fitness to levels which should help them run from the fastest cat in your home.


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