Gene injection directly into brain could cure alcoholism: monkey study

Monkeys share many traits with humans — including our thirst for alcohol.

Medical researchers were able to turn eight rhesus macaque monkeys into heavy drinkers by offering them increasing concentrations of alcohol.

With free access to booze all day over a period of six months, it wasn’t long before the monkeys were true party animals, binge drinking on a regular basis.

The purpose of the research was to test a type of gene therapy — currently used to treat Parkinson’s disease — in the hope that it might someday help people with severe alcoholism.

“We know that we can get people with alcohol use disorder to stop drinking for short periods of time” with drugs, Kathleen Grant, a neuroscientist at Oregon Health & Science University, told Wired. “But the desire to drink again often supersedes taking their medications.”

Grant and a team from several other research centers injected a gene therapy into the brains of four of the eight alcoholic monkeys. The injections contained a growth factor protein called glial cell line-derived neurotrophic factor, or GDNF.

Earlier studies have shown that GDNF can stimulate the production of dopamine, a neurotransmitter in the brain that plays a role in rewarding addictive behavior.

So, Grant and her colleagues used magnetic resonance imaging to guide the injection of GDNF into the ventral tegmental area of the brain, where neurons are located that make dopamine and distribute it throughout the brain.

“This was incredibly effective,” Grant said in a news release. “Drinking went down to almost zero.

“For months on end, these animals would choose to drink water and just avoid drinking alcohol altogether,” she added. “They decreased their drinking to the point that it was so low we didn’t record a blood-alcohol level.”

Moreover, the GDNF treatment has long-lasting benefits. After a year, alcohol use among the four treated monkeys dropped by more than 90%, compared to the control group of monkeys that didn’t receive the treatment.

“It was as if they were learning that the alcohol just wasn’t something they wanted to engage in anymore,” Grant said.

Dopamine plays a critical role in alcoholism. “Dopamine is involved in reinforcement of behavior, and in people finding certain things pleasurable,” Grant said.

“Acute alcohol use can increase dopamine. However, by drinking it chronically, the brain adapts in such a way that it decreases the release of dopamine,” she added.

“So when people are addicted to alcohol, they don’t really feel more pleasure in drinking. It seems that they’re drinking more because they feel a need to maintain an intoxicated state.”

The procedure isn’t yet ready for human trials, and even if it were used in humans, this kind of brain surgery would only be used in the most severe cases of alcoholism.

That’s partly because the treatment is irreversible and permanently alters the brain, raising medical as well as ethical issues.

“It would be most appropriate for people who have already shown that all our normal therapeutic approaches do not work for them,” Grant said. “They are likely to create severe harm or kill themselves or others due to their drinking.

“This would be a last resort if all other treatment options fail.”

Alcoholism is a significant problem in the US and around the world, with an estimated 30 million Americans living with alcohol use disorder, according to the National Institute on Alcohol Abuse and Alcoholism.

The study, published in Nature Medicine, was also supported by researchers from Wake Forest University School of Medicine, Ohio State University and the University of California, San Francisco.