Study Proves Gene Therapy to Curtail Urge to Drink in Rodents

Experiments on mice suggest that gene therapy may help reduce long-term drinking, say researchers.

Published in Alcoholism: Clinical & Experimental Research, the study shows that just as the risk of developing alcoholism is strongly influenced by genetic factors, mutations in gene coding, such as the aldehyde dehydrogenase (ALDH2) allele, may also protect against this risk.

During the study, rodents bred as heavy alcohol drinkers were administered an anti-Aldh2 antisense gene, which curtailed their urge to drink.

“An ‘experiment of nature’ is observed in some individuals of East Asian origin, who are 66 to 99 percent protected against alcoholism,” said Yedy Israel, professor of pharmacological and toxicological chemistry at the Universidad de Chile, and adjunct professor of pathology, anatomy and cell biology at Thomas Jefferson University in Philadelphia.

“These individuals carry a genetic mutation that inactivates the aldehyde dehydrogenase-2 enzyme, which is needed to eliminate products of alcohol metabolism. When they drink, they experience nausea, facial redness and a pounding heart,” the researchers added.

Richard Deitrich, Professor Emeritus at the University of Colorado School of Medicine, considers gene therapy to be a cutting edge technique in terms of alcohol research.

“Gene therapy is a technique that has been proposed for a number of human conditions, mostly to correct inborn errors that lead to severe conditions,” he said.

“In terms of alcohol research, however, this is certainly ‘cutting edge.’ The goal here is to silence a gene or at least impair its function, thereby mimicking a genetic condition that some Asian individuals normally have that protects them from developing alcoholism,” he added.

For their study, the researchers bred rats as heavy alcohol drinkers, and then further rendered them alcohol dependent through a two-month period of unlimited, voluntary intake of the equivalent of premium beer.

The researchers also scheduled a one-hour “happy hour” for the rodents each day, during which the animals drank 10 times more alcohol than what is normally consumed.

An anti-Aldh2 antisense gene was then intravenously administered, with the intent of “shutting off” ALDH2 activity.

“Animals that were given a single intravenous injection of the antisense gene therapy reduced their consumption by one half, for a full month, which was the duration of the study. This would appear to have implications for a social-drinking pattern, and the notion of ‘harm reduction,’ where full abstinence is not the only acceptable goal,” said Israel.

Israel’s team is now planning to examine methods by which they may deliver genes through a single treatment that can last for a period of one year to a lifetime.

“Given that the main problem in the pharmacological treatment of alcoholism is that patients do not adhere to the treatment, and that the effect of most recent medications is only moderate at best, gene therapy shows great potential value for the treatment of alcoholism. A rapid transfer of gene-therapy possibilities into the clinic will depend on how these new studies proceed,” Israel said.

Deitrich said that the findings were a long way from being applied to humans.

He, however, added: “This is a remarkable paper and, even if these studies are never translated to humans, it is an important addition to the alcohol- research field.”

Source-ANI
KAR/P