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Mario López Oliva

domingo, 3 de agosto de 2008

AICAR: Scientists say they've put exercise in a pill

Salk Institute for Biological Studies
Ronald Evans holds a vial of a drug that boosts the effects of exercise in mice. Evans works at the Salk Institute for Biological Studies in La Jolla, Calif.
Researchers experiment with a chemical compound that they say can produce the benefits of aerobic activity without the work.
By Alan Zarembo, Los Angeles Times Staff Writer
August 1, 2008

Scientists have discovered what could be the ultimate workout for couch potatoes: exercise in a pill.

In experiments on mice that did no exercise, the chemical compound, known as AICAR, allowed them to run 44% farther on a treadmill than those that did not receive the drug.

The drug appeared to change the physical composition of muscle, essentially transforming the tissue from sugar-burning fast-twitch fibers to fat-burning slow-twitch ones, the same change that occurs in distance runners and cyclists through training, according to research released Thursday.

"You're getting the benefits of exercise without having to do any work," said David Mangelsdorf, a pharmacologist at University of Texas Southwestern Medical Center in Dallas, who was not connected with the research.

It is unknown if the drug has any benefit for athletes who actually work out -- or for any human, for that matter, since the research has so far only involved mice.

Though the chemical pathways that transform muscle cells appear to be the same in mice and humans, Michael Rennie, a physiologist at the University of Nottingham in England, said that AICAR did not activate human pathways at the doses research subjects received in a study he conducted of the drug's potential to treat diabetes.

"Mice are not men," Rennie said. "Rats and mice are much more metabolically unstable than human beings."

Nonetheless, lead researcher Ronald Evans, a molecular physiologist at the Salk Institute for Biological Studies in La Jolla, said he has already been contacted by dozens of athletes and overweight people who have heard about his research from lectures.

One request came from a horse trainer who was interested in trying AICAR out on a thoroughbred, he said. Evans declined.

"Anything that could provide half of a quarter of 1% is attractive," said Dr. Don Catlin, a professor emeritus of molecular and medical pharmacology at UCLA and a top anti-doping expert. "The athlete who can find a way to get an edge is one up on his competitors."

Evans said he had notified world anti-doping officials, who are now scrambling to implement a test for it before the Beijing Olympics start next week.

The compound, which is naturally produced in tiny amounts in human muscle cells and has been studied for decades, is readily available through scientific supply companies. One company was offering AICAR for $120 a gram. At that price, giving a person the drug in the same concentration the mice got would cost thousands of dollars a day.

Evans predicted that in the wake of his study, published in the journal Cell, the drug would "fly off the shelves."

AICAR has been tested in humans for a variety of conditions. "It was found to be a quite safe drug, at least at the doses we were using," said chemist Paul Laikind, who began testing it in the 1980s as a means of preserving blood flow to the heart during surgery.

Drug maker Schering-Plough Corp. is trying to develop it as an intravenous infusion for use during bypasses.

With more research, scientists said, the drug's fat-burning properties could also help reduce weight, ward off diabetes, prevent heart disease and restore the fitness of bedridden patients.

The discovery of AICAR as a potential couch-potato exercise pill grew out of Evans' continuing research on the physiology of muscle cells.

In 2004, he made headlines for engineering "marathon mice." By injecting a single gene into the nucleus of a fertilized egg, he created mice born with more efficient muscles, faster metabolisms and stronger hearts.

Evans wanted to know if it was possible to achieve the same effect using a drug.

His team started not with AICAR but with another compound known as GW1516, which drug maker GlaxoSmithKline is trying to develop to raise levels of HDL, or good cholesterol. The drug is known to stimulate the production of a protein known as PPARd, which in turn activates the genes that boost endurance in muscle cells.
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