July 31, 2008
While steroids can give the boost in muscle power that so often tempts athletes to abuse these drugs, researchers say there hasn’t been a targeted drug capable of building the endurance needed to run a marathon or ride a bike through the Alps.
Now there might be, suggests a new study with mice. And that’s creating both hope and worry.
The study found that a drug 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 another chemical endowed mice with greater endurance, even without the workout.
“It’s tricking the muscle into ‘believing’ it’s been exercised daily,” said Ronald Evans of the Salk Institute in La Jolla, Calif. Both compounds “are very logical targets for athletic abuse, and we need to be aware of that.” But for people with health problems that preclude much exercise, the findings could be a boon, he added.
The study by Evans and colleagues appears in the July 31 online issue of the research journal Cell.
Evans said his group has already spoken to the World Anti-Doping Agency and is developing a test aimed at detecting use of the PPARd-boosting drug. That test won’t be available in time for this summer’s Olympic games, he said. It also wouldn’t detect the use of AICAR, a chemical that is available but isn’t an FDA-approved drug.
Earlier studies had found that a red wine ingredient called resveratrol could build endurance, but only at enormous doses and by uncertain means. The chemicals tested in the new study are thought to work by specifically tapping into the molecular mechanisms that normally “reprogram” muscle genes in response to exercise.
Evans said it’s not certain that athletes could get a boost from the drugs: the effects in mice might not work as well in highly trained people who may be “pushing the limits” already.
Skeletal muscle, the type of muscle that moves the body, comes in two main types: 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.
Evans’ team had previously found they could genetically engineer, or “pre-program” mice to produce more of the fat-burning slow-twitch muscle fibers, turning them into “marathon mice” with 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 skeletal muscle metabolism.
But could you re-program rather than pre-program muscles by simply giving a drug that acts on PPARd? To find out, the researchers gave mice an experimental drug, known only as GW1516, that increases PPARd activity. The drug is being tested for the treatment of metabolic disease, but Evans wanted to know its effects on muscle. “It was a spectacular failure,” he said. It “had no impact on running ability” even though there were changes in muscle gene activity.
Something was missing, so the scientists took a different tack. They gave the PPARd drug to mice that were undergoing exercise training. The same dose and duration of GW1516 treatment that previously failed to alter performance, when paired with four weeks of exercise training, increased the animals’ running time by 68 percent and their running distance by 70 percent over other trained mice, the new study reports.
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. That pattern bore a striking resemblance to the one seen years earlier in the genetically engineered marathon mice, they noted.
Since PPARd on its own wasn’t enough, the researchers decided to try one more thing: a chemical known as AICAR that was known to act on a protein in the body called AMPK. Evans’ group suspected AMPK might be the link between exercise and PPARd.
To their surprise, even in sedentary mice, four weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44 percent. “We were blown away that AICAR alone mimicked exercise—not to the same level but a healthy boost,” Evans said.
“We revealed that synthetic PPARd activation and exercise or more importantly AMPK activation alone… re-programs the skeletal muscle genome and dramatically enhances endurance,” the researchers wrote. “We believe that the strategy of re-organizing the preset genetic imprint of muscle (as well as other tissues) using exercise mimetic drugs has therapeutic potential in treating certain muscle diseases such as wasting and frailty as well as obesity where exercise is known to be beneficial.”
Source: http://www.world-science.net
While steroids can give the boost in muscle power that so often tempts athletes to abuse these drugs, researchers say there hasn’t been a targeted drug capable of building the endurance needed to run a marathon or ride a bike through the Alps.
Now there might be, suggests a new study with mice. And that’s creating both hope and worry.
The study found that a drug 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 another chemical endowed mice with greater endurance, even without the workout.
“It’s tricking the muscle into ‘believing’ it’s been exercised daily,” said Ronald Evans of the Salk Institute in La Jolla, Calif. Both compounds “are very logical targets for athletic abuse, and we need to be aware of that.” But for people with health problems that preclude much exercise, the findings could be a boon, he added.
The study by Evans and colleagues appears in the July 31 online issue of the research journal Cell.
Evans said his group has already spoken to the World Anti-Doping Agency and is developing a test aimed at detecting use of the PPARd-boosting drug. That test won’t be available in time for this summer’s Olympic games, he said. It also wouldn’t detect the use of AICAR, a chemical that is available but isn’t an FDA-approved drug.
Earlier studies had found that a red wine ingredient called resveratrol could build endurance, but only at enormous doses and by uncertain means. The chemicals tested in the new study are thought to work by specifically tapping into the molecular mechanisms that normally “reprogram” muscle genes in response to exercise.
Evans said it’s not certain that athletes could get a boost from the drugs: the effects in mice might not work as well in highly trained people who may be “pushing the limits” already.
Skeletal muscle, the type of muscle that moves the body, comes in two main types: 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.
Evans’ team had previously found they could genetically engineer, or “pre-program” mice to produce more of the fat-burning slow-twitch muscle fibers, turning them into “marathon mice” with 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 skeletal muscle metabolism.
But could you re-program rather than pre-program muscles by simply giving a drug that acts on PPARd? To find out, the researchers gave mice an experimental drug, known only as GW1516, that increases PPARd activity. The drug is being tested for the treatment of metabolic disease, but Evans wanted to know its effects on muscle. “It was a spectacular failure,” he said. It “had no impact on running ability” even though there were changes in muscle gene activity.
Something was missing, so the scientists took a different tack. They gave the PPARd drug to mice that were undergoing exercise training. The same dose and duration of GW1516 treatment that previously failed to alter performance, when paired with four weeks of exercise training, increased the animals’ running time by 68 percent and their running distance by 70 percent over other trained mice, the new study reports.
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. That pattern bore a striking resemblance to the one seen years earlier in the genetically engineered marathon mice, they noted.
Since PPARd on its own wasn’t enough, the researchers decided to try one more thing: a chemical known as AICAR that was known to act on a protein in the body called AMPK. Evans’ group suspected AMPK might be the link between exercise and PPARd.
To their surprise, even in sedentary mice, four weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44 percent. “We were blown away that AICAR alone mimicked exercise—not to the same level but a healthy boost,” Evans said.
“We revealed that synthetic PPARd activation and exercise or more importantly AMPK activation alone… re-programs the skeletal muscle genome and dramatically enhances endurance,” the researchers wrote. “We believe that the strategy of re-organizing the preset genetic imprint of muscle (as well as other tissues) using exercise mimetic drugs has therapeutic potential in treating certain muscle diseases such as wasting and frailty as well as obesity where exercise is known to be beneficial.”
Source: http://www.world-science.net
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