A new gene therapy for alcohol addiction has shown impressive results in a study in monkeys. If these results translate to human trials, we could be looking at a whole new way of treating severe alcohol dependency.
Alcohol use disorder (AUD) is a challenging condition to treat, with huge implications for the physical and mental health of patients and their loved ones. It’s common for people in recovery from AUD to relapse, so scientists are looking for treatments that might be able to break this cycle.
Recent years have seen promising trials of pharmaceutical treatments, including the psychedelic compound psilocybin, to help people with alcohol dependence to cut down on their drinking, but a new study has started to explore a therapy with the potential for even better – and possibly permanent – results.
This new gene therapy approach centers around the brain’s reward circuitry, mediated by the feelgood neurotransmitter dopamine. A protein called glial-derived neurotrophic factor, or GDNF, is important for keeping the neurons within this circuitry functioning, but levels have been found to be reduced in people with AUD during periods of abstinence, most obviously in a region of the brain called the ventral tegmental area (VTA).
The researchers hypothesized that using gene therapy to deliver more GDNF to the cells of the VTA could help reinforce the dopaminergic signaling and avoid a relapse.
The study involved eight rhesus macaque monkeys that underwent an induction period where they were exposed to increasing concentrations of alcohol. After the induction phase, the monkeys had free access to alcohol and water for 21 hours per day for a period of 6 months, during which they developed heavy drinking behaviors, followed by an abstinence phase that lasted 12 weeks.
The gene therapy was delivered to half of the monkeys via a viral vector containing a copy of the human GDNF gene, injected directly into the VTA. The results were remarkable.
“Drinking went down to almost zero,” said co-senior author Dr Kathleen Grant, a professor at Oregon Health & Science University, in a statement. “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.”
The researchers explained how acute alcohol consumption in people who aren’t addicted leads to the release of dopamine, which is why it gives us a pleasurable buzz – sometimes a bit too much for our own good!
With chronic alcohol use, though, the brain adapts and stops releasing so much dopamine. “So when people are addicted to alcohol, they don’t really feel more pleasure in drinking,” said Grant. “It seems that they’re drinking more because they feel a need to maintain an intoxicated state.”
One of the key advantages of gene therapy is that it offers a potentially permanent solution, which could bring hope for people with the most severe cases of AUD. It remains a significant health challenge; according to the National Institute on Alcohol Abuse and Alcoholism, 29.5 million people in the US had AUD in 2021, including 894,000 young people aged 12-17.
The GDNF viral vector therapy is already used in some patients with Parkinson’s disease, and UMass Chan Medical School neuroscientist Miguel Sena-Esteves, who was not involved in the research, commented on the safety of the treatment in a briefing published alongside the study: “Of note is the apparent safety of continuous GDNF expression in the VTA, as there were no serious adverse events in any of the test subjects.”
It may be some time before human trials show whether this approach will be feasible in the clinic, but it’s a very positive first step towards a new dawn for a condition that the journal’s editorial team describe in the briefing as “a substantial unmet clinical need worldwide.”
The study is published in Nature Medicine.
Source Link: New Gene Therapy Cuts Drinking In Alcohol-Dependent Monkeys By 90 Percent
