Gene therapy injection into the brain causes alcohol use disorder to stop — in monkeys

A new gene therapy that "resets" the brain's reward system could help treat alcohol use disorder, a new study in monkeys suggests. 

In monkeys who tend to drink heavily when provided lots of alcohol, surgically injecting a gene therapy into the brain increased the production of the so-called feel-good hormone dopamine, the study showed. This, in turn, dramatically reduced the primates' alcohol consumption, the effects of which were sustained over a year. 

If safe and effective in humans, the therapy could provide a "one-time" treatment for alcohol use disorder (AUD), a medical condition in which patients can't stop or control their drinking despite it negatively impacting their daily life. Excessive drinking causes 140,000 deaths a year in the U.S., and although AUD is one of the most common psychiatric disorders, only three drugs for it have been approved by the U.S. Food and Drug Administration (FDA). 

None directly target the underlying brain changes seen with sustained heavy drinking. 

Related: What does alcohol do to the body?

Alcohol boosts the brain's production of dopamine, which leads to feelings of relaxation and improved mood. However, in AUD, the brain adapts by producing less dopamine on its own, meaning people need to drink more to achieve the same positive effects.  

That's also true in monkeys that drink heavily, even during periods when they aren't consuming any alcohol, study lead author Kathleen Grant, a professor of behavioral neuroscience at Oregon Health & Science University, told Live Science.  

In the new study, published Monday (Aug. 14) in the journal Nature Medicine, Grant's team injected a genetically modified virus into the ventral tegmental area — a region in the brain involved in reward processing — of four monkeys as part of a surgical procedure. Those monkeys had been given access to increasingly higher amounts of ethanol dissolved in water over several months to the point where their consumption levels simulated chronic alcohol binge drinking in humans. 

Using a similar approach to what has already been used to treat Parkinson's disease and a rare genetic disorder known as aromatic L-amino acid decarboxylase deficiency, the harmless virus carried a gene that encodes the protein glial cell line-derived neurotrophic factor (GDNF), which helps preserve and regrow neurons. By putting the GDNF gene into cells that make dopamine, the team assumed it would spur them to produce normal levels of the chemical. 

The monkeys reduced their alcohol consumption by more than 90% compared with controls, and their dopamine levels were restored to "normal levels" for at least a year after treatment, roughly equivalent to nine to 12 years in human time, Grant said. Because relapse is such an "integral part of the cycle" of AUD, getting back to levels the animals had before they started drinking heavily is crucial, she emphasized. 

Andrew Mcquillin, a professor of molecular psychiatry at University College London who was not involved in the research, told Live Science in an email that the long-term side effects of this treatment are still unclear. Although brain surgery is "generally well-tolerated" in humans, he said it "seems a somewhat invasive approach for all but the most severe cases of alcohol use disorder."

Grant also urged caution in over-generalizing the findings. "This is only proof-of-principle that it is possible to reverse this behavior in people with drinking disorders that are resistant to all other treatments," she said. "This would not be your first line of treatment, [it] would be appropriate only for very severe cases of alcohol use disorder."

Mcquillin added that future studies will be needed to test the acceptability of this treatment for substance use disorders. The findings could, however, open doors for other treatment options. 

"There is also the possibility that new or existing small molecules that mimic the therapeutic mechanism in this study may represent new treatment targets for substance use disorders," he said.