Wednesday, January 09, 2008

Gene Therapy for Alcoholics

An interesting approach to curbing alcoholism is tested on rats.

By Anna Davison

Alcoholic animals: Researchers in Chile have used gene therapy to curb drinking in alcoholic rats. Credit: U.S. National Park Service

Researchers in Chile have succeeded in keeping the drinking habits of alcoholic rats in check using gene therapy. The treatment mimics a natural mutation common in East Asian people, which lowers their tolerance to alcohol, making them less likely to become alcoholics.

According to the National Institutes of Health, 17.6 million people abuse alcohol or are alcohol dependent in the United States alone. If the gene-therapy technique could be applied to humans, scientists say that it may be a valuable addition to the drugs and behavioral approaches currently used to treat alcoholism.

The gene therapy works in a similar way to a drug currently used to treat alcoholics, which is effective but unpopular with patients, many of whom stop taking it.

"It's great when innovative approaches are being used for treatment, because we need them," says George Koob, codirector of the Pearson Center for Alcoholism and Addiction Research, at the Scripps Research Institute. He was not involved in the work in Chile.

The gene therapy, described in the latest issue of the journal Alcohol: Clinical and Experimental Research, curbed the activity in the liver of an enzyme--aldehyde dehydrogenase--that plays a major role in metabolizing alcohol. Nearly a third of East Asians have a natural genetic mutation that has the same effect, so when they drink, their faces turn red, their hearts pound, and they feel sick--all good incentives to go easy on alcohol.

The gene therapy tested by Yedy Israel, a professor of pharmacological and toxicological chemistry at the University of Chile, and his colleagues triggers the same unpleasant response to alcohol in rats.

"It's a new way of doing an old thing," Koob says. "I think it's very clever and very interesting."

The researchers in Chile started with rats bred for their alcoholic tendencies and offered them unlimited quantities of diluted ethanol--the equivalent of higher-alcohol premium beer--for two months to make them even more dependent. The researchers then cut off the animals' access to alcohol and injected some of them with a virus containing a gene that inhibits aldehyde dehydrogenase.

Three days later, the researchers implemented a month of daily "happy hours," letting the rats drink as much as they wanted. In an hour, each of the animals put away the equivalent, in human terms, of about seven premium beers--10 times more alcohol than what was put away by alcoholic animals that hadn't been through the two-month dependency regimen.

During the first happy hour, rats that were given gene therapy "didn't realize they were going to feel bad, and they drank a tremendous amount," Israel says. Afterward, "the animals clearly didn't look comfortable." Those rats then markedly reduced their alcohol consumption on subsequent days. Over the course of the happy hours, they drank half as much, on average, as the untreated animals. The effect lasted throughout the monthlong study.