Gene Therapy Curbs Alcoholic Behavior
> 1/9/2008 1:54:01 PM

Working from the model of an obscure genetic variation responsible for alcohol intolerance among those of East Asian descent, researchers recently succeeded in curbing the addictive urges of alcoholic rats.

Most individuals, while obviously subject to the many physical repercussions of alcohol consumption, only display relevant symptoms after drinking well past the point of intoxication; allergic reactions to alcohol are rare. But approximately 1/3 of East Asian patients bear the aforementioned irregularities in an enzyme that factors heavily in the liver's oxidation of alcohol. Acetaldehyde, or the product of that oxidation, can interfere with the body's internal processes if present in significant quantities, and bodies affected by this polymorphic variation produce far more of the substance, creating a hypersensitivity to all forms of alcohol. After consuming even moderate amounts of the substance, affected patients grow flushed and nauseous, their uneven heart rates rising to uncomfortably high levels. This common affliction, if it could be called that, receives a large share of credit for the lower-than-average levels of alcoholism observed among those of East Asian ancestry.

Researchers in Chile
worked with a group of rats who'd been conditioned toward a dependence on alcohol in order to determine whether inducing a genetic variation similar to that held by drink-averse Asians would discourage their reliance on the substance and lead them to modify their behavior accordingly. These rats, already well-bred alcoholics, had been plied with unlimited quantities of diluted ethanol for several weeks in order to intensify their addictions prior to the study. Researchers then injected some of the rats with a viral gene that works to contain the production of acetaldehyde and discontinued their access to alcohol for three days. Once they were certain the viruses had taken effect, researchers again supplied the rats with their substance of choice and observed their subsequent behaviors. Withdrawal and dependence initially led these animals to consume even more than usual, and those who'd been dosed began to display symptoms of severe discomfort shortly after drinking. After enduring this physical trauma, even the addicted rates grew more wary of the substance, gradually reducing their intake and drinking, on average, less than half the quantity consumed by the control rats during the month-long study.

This approach is not entirely new: the anti-alcohol drug disulfiram, or Antabuse, works in a fashion similar to the genetic injections received by these rats by blocking the oxidation of alcohol at the aceteldehyde stage, leading to an abnormally high amount of the chemical in the bloodstream and producing a similarly undesirable reaction. Disulfiram is understandably unpopular with alcoholics because of the pronounced physical discomfort it brings about, and noncompliance is extremely common. Immediate and total abstinence is very rarely an option for the extreme alcoholics who receive this medication due to the painful symptoms of withdrawal, and the drug may only reinforce the severity of their condition and discourage their attempts to beat the addiction. One assumes that the pains of dependence and resulting hangovers are, for some reason, preferable to the profound unpleasantness induced by these drugs. The rats in the study, given a choice, would almost certainly refuse the injections and continue to drink themselves into a destructive stupor every day.

For that reason, experts in the addiction field view this development as "interesting" but hold their outright praise of a prospective approach that is still in its earliest developmental stages. Researchers have proposed a full genetic treatment that would effectively create a lifelong alcohol allergy, but addicts who've experienced the disulfarim effect before would almost certainly hesitate to receive this therapy. Still, a long-term treatment may prove more effective than daily medication, and it could be designed to last only a few weeks or months. As most substance abusers know, true addiction leaves one very susceptible to impulsive and profoundly unhealthy behavior, making voluntary treatment plans all but impossible. This sort of invasive gene therapy may never come into common practice, but it can, at the very least, serve to inform more effective approaches. If reducing an alcoholic's desire to drink is not a solution, we may have to make the substance itself intolerable to them. And it won't be pretty, but those who've hit rock bottom and begun to reach out for help need all the treatment options they can get.

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