Injecting Gene Therapy into the Brain as a Potential Treatment for Alcohol Misuse

A one-time gene treatment administered into the brains of alcoholics reduced their drinking in a limited trial with monkeys.

The signalling molecule dopamine, which has been linked to addiction, saw an increase in synthesis as a result of the gene therapy. Because of the potential dangers to the brain, this treatment, should it prove effective in humans, would likely be reserved for the most extreme cases of alcohol abuse.

Talk therapies are currently the mainstay of therapy for alcohol abuse. Some medications can be used to help people drink less, but they aren’t effective for everyone.

Some alcoholics who try to quit find that their desires for alcohol are too strong for them to continue taking cessation aids. Kathleen Grant and her colleagues at Oregon Health & Science University in Portland considered the possibility that gene therapy could be an effective, long-term treatment.

Dopamine levels in the ventral tegmental areas, located roughly in the centre of the brain, are commonly reduced in chronic alcoholics. As a result, “this contributes to people needing alcohol for [feelings of] reward,” says Grant. Her group consequently developed a gene treatment to increase dopamine in these regions.

Rhesus monkeys were used to evaluate the method. These teenage monkeys drank heavily when given the option of not doing so. As adults, they voluntarily drank the equivalent of several drinks per day.

Four of these monkeys had the gene for glial cell line-derived neurotrophic factor (GDNF), a signalling molecule, introduced into their brains using a modified virus by Grant’s team. Dopamine-producing brain cells are hypothesised to benefit from GDNF’s ability to prolong their viability and performance.

Two tiny incisions were made in the patient’s skull, and the infusion was injected into the ventral tegmental regions. A control group of four animals was given a placebo.

The treated animals voluntarily consumed over 90% less alcohol than the control group over the following 12 months. According to Grant, “they cut down to almost zero” on their drinking.

The animals were euthanized at year’s end, and their brains were studied. The treated rats showed increased GDNF and dopamine levels in the affected brain areas, relative to the control group.

Grant acknowledges that the mechanism of action of the therapy remains mysterious. Dopamine production in brain cells might increase, or its clearance might be slowed. Levels of serotonin and noradrenaline (norepinephrine) were also increased due to the GDNF.

Although the method itself is excellent, clinicians may be hesitant to use it unless the patient has a severe alcohol use disorder, according to Simon Waddington of University College London. As one person put it, “It’s a heck of a thing to have an injection into your brain of a gene therapy that you can’t switch off.”