Couch-Potato Drugs Are WADA’s First Banned for Gene-Doping Ties

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Jan. 14 (Bloomberg) -- Two drugs that activate genetic switches, fooling the body into believing it has exercised, are the first to be added to the Olympic sports prohibited list for their ties to gene doping.

The drugs, whose effects were first disclosed in a report published online by the journal Cell on July 31, were added to the nine-page list issued by the World Anti-Doping Agency under the “Gene Doping” classification as of Jan. 1.

It’s a category that is likely to grow over the next five to 10 years, said Dr. Gary Wadler, who heads WADA’s Prohibited List Committee, as gene therapy becomes “part of the matrix of what physicians have to treat patients.”

“There’s gene-therapy stuff going on in research labs everywhere in the world,” Wadler said in an interview at his Manhasset, New York, office. “I think they’re going to cause breakthroughs, and those breakthroughs, if they have any application to enhance athletic performance, then you’ll ultimately see it banned.”

One of the drugs is a synthetic protein called Aicar that, when given to mice, improved endurance by 44 percent after four weeks, even without exercise. The other is an experimental medicine made by GlaxoSmithKline Plc, GW1516, which remodeled the mice’s skeletal muscle and raised their endurance levels by 75 percent when the animals also ran on a treadmill.

WADA’s 2009 prohibited list includes nearly 70 anabolic steroids; about 60 stimulants; hormones; diuretics and other masking agents; blood-doping methods; and several narcotics. The Montreal-based agency oversees anti-drug programs for Olympic- level sports.

2002 Prediction

Wadler said he “predicted the future” when in 2002 he wrote a chapter on emerging science and technologies for the textbook “Performance Enhancing Substances in Sport and Exercise.” In it, he discussed the implications of the U.S. Human Genome Project, which was launched in 1990, and examined gene transfer therapy.

“The dissection of the human genetic code not only opened a Pandora’s box of diagnostic tools and methods; it has significantly paved the way for an array of therapeutic interventions never conceived before and has spawned the field of pharmacogenetics,” he wrote at the time.

WADA held a gene-doping workshop for scientists, ethicists, athletes and representatives from the Olympic movement in March 2002 and again in December 2005 and June 2008. It formed its expert panel on gene doping in 2004.

‘Couch Potato’

Last July, a news release, titled “Exercise in a Pill,” announced the results of the study by the Salk Institute for Biological Studies in San Diego that detailed the effects of Aicar, which it called the “ultimate couch-potato experiment,” as well as the effects of GW1516.

The findings may lead to the development of obesity and muscle-wasting-disease treatments, and has implications for the treatment of diabetes and lipid disorders.

By activating different genetic switches with the two drugs, the scientists were able to increase fat burning and the mice showed major transformation of skeletal muscle fibers. In giving the mice GW1516 and a regular exercise regimen, for example, they saw a 38 percent increase in “slow twitch” muscle fibers, which relate to a muscle’s endurance.

“They have the capacity of changing the patterns of gene expression in cells and tissues, so our view is that that’s a form of gene manipulation,” Theodore Friedmann, chairman of WADA’s Gene Doping Panel, said in a telephone interview. “I don’t think that list is going to shrink. It’s probably going to increase markedly over the years.”

Test Procedures

Ronald Evans, who is a professor in the Salk Institute’s Gene Expression Laboratory and led the research into the use of Aicar and GW1516 to manipulate signaling pathways, also developed a test to readily detect the drugs in blood and urine, and is working with WADA to enact its implementation.

While these drugs can be easily detected, other gene- therapy methods are much more problematic for WADA, and in turn sports associations and leagues. These involve the use of genetic techniques to bring doping substances to muscle tissue and other targets without passing through blood and urine, thereby confounding testing efforts.

“It’s better for patients, but it also makes it more challenging because of doping,” Wadler said.

Friedmann, who runs a gene-therapy laboratory at the University of California, San Diego, said WADA has mounted a major research program to develop ways to find evidence of gene manipulation.

Drug’s Effect

“WADA is very forward-looking into designing new forms of doping detection based on the new principle that you don’t look for the drug itself, you look for the effect of the drug,” said Friedmann.

In February, the committee will begin reviewing the 2009 list, assessing research and what they’ve learned about doping through everything from medical journals to police investigations. They’ll then tweak the list and turn it over to WADA’s Executive Committee for final approval Oct. 1, giving sports organizations three months to adopt new regulations and understand the changes.
By Mason Levinson