Parkinson's gene therapy works on alcoholism too

To do so, researchers injected a non-harmful virus carrying a protein called glial-derived neurotrophic factor, or GDNF, into the brains of a group of rhesus macaque monkeys who heavily consumed ethanol diluted in water. After four macaques received the procedure, their ethanol consumption decreased by over 90 percent compared to the control group.

"Drinking went down to almost zero," Grant said. "For months on end, these animals would choose to drink water and just avoid drinking alcohol altogether. They decreased their drinking to the point that it was so low we didn't record a blood-alcohol level," she added.

GDNF is a growth factor that boosts the activity of dopamine-synthesizing neurons in the brain by promoting cell proliferation. Dopamine is a neurotransmitter that promotes feelings of well-being and happiness in the brain. However, in alcohol use disorder, dopamine release is reduced due to prolonged alcohol consumption.

"Dopamine is involved in [the] 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. 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," she added.

Results were incredible

And the results were incredible. "The monkeys that were treated with this gene permanently started overexpressing dopamine, and they decreased their drinking substantially," Grant said.

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

You can view the study for yourself in the journal Nature Medicine.

Study abstract:

"Alcohol use disorder (AUD) exacts enormous personal, social, and economic costs globally. Return to alcohol use in treatment-seeking patients with AUD is common, engendered by a cycle of repeated abstinence-relapse episodes even with the use of currently available pharmacotherapies. Repeated ethanol use induces dopaminergic signaling neuroadaptations in ventral tegmental area (VTA) neurons of the mesolimbic reward pathway, and sustained dysfunction of reward circuitry is associated with a return to drinking behavior. We tested this hypothesis by infusing adeno-associated virus serotype 2 vector encoding human glial-derived neurotrophic factor (AAV2-hGDNF), a growth factor that enhances dopaminergic neuron function, into the VTA of four male rhesus monkeys, with another four receiving vehicle, following induction of chronic alcohol drinking. GDNF expression ablated the return to alcohol-drinking behavior over 12 months of repeated abstinence–alcohol reintroduction challenges. This behavioral change was accompanied by neurophysiological modulations to dopamine signaling in the nucleus accumbens that countered the hypodopaminergic signaling state associated with chronic alcohol use, indicative of therapeutic modulation of limbic circuits countering the effects of alcohol. These preclinical findings suggest gene therapy targeting relapse prevention may be a potential therapeutic strategy for AUD."