Experimental treatment eliminates alcoholism in monkeys

Alcohol consumption is associated with many health problems. It’s estimated that, every year, more than two million people die across the world because of it.

On Monday, the journal Nature Medicine published a novel approach to treat the most serious cases of addiction to this substance: gene therapy. This type of treatment uses innocuous viruses as vehicles — they insert instructions into a patient’s cells, which allows for the production of proteins that can correct a problem.

Gene therapy is already being used to treat certain types of cancer, hemophilia, rare diseases and even Parkinson’s. Now, a group of scientists from the Oregon Health and Science University has tested a particular type of gene therapy — which is already used against this neurological disease — to measure its potential effectiveness against alcoholism.

When Parkinson’s develops, neurons that produce dopamine — a multifunctional neurotransmitter often associated with motivation and pleasure — begin to die. Without this element, the body loses control of movement and the most well-known symptoms of the disease appear. One of the treatment options for this condition is the insertion of the growth factor GDNF into the brain via surgery, as well as gene therapy to accelerate the growth of neurons that produce dopamine.

In the case of alcoholism, the substance is known to increase dopamine levels — something that makes the drinker feel good and reinforces pleasure. However, chronic alcohol consumption causes the brain to get used to it and stop generating dopamine, which also kills the pleasant sensation of drinking. The study’s authors — led by Kathleen Grant, director of the division of neuroscience at the Oregon National Primate Research Center — posited that restoring balance in dopamine production would help reduce alcohol consumption. They tested their hypothesis in monkeys.

The experiment was carried out with eight macaques, who were given a large amount of ethanol-laced water to generate alcoholism. Later, four of them received treatment with gene therapy, while the other four received only a placebo. The four animals that received the growth factor GDNF saw how the reward system that regulates dopamine was restored to balance in their brain: they reduced their alcohol consumption by 90% compared to the control group. “Its consumption was reduced until it almost disappeared. For months, they chose only water and avoided alcohol. It was incredibly effective,” says Grant.

A costly treatment

There’s still a long road ahead to treating people addicted to alcohol with this system. On the one hand, this type of treatment is usually very expensive: it would only be applied when other, more conventional strategies fail. Additionally, this system requires surgery — something that also doesn’t facilitate its widespread application. Finally, the authors warn of potential limitations, such as the possibility of generating problems due to an excess of dopamine in the brain.

“While beneficial in the context of binge drinking, increased dopamine may be detrimental to other behaviors, such as stimulant use disorders,” they write in Nature Medicine. Previous studies have shown that an overexpression of GDNF in the same region of the brain treated in this experiment can increase the chances of relapse, particularly when it comes to cocaine addiction.

However, those responsible for the study still suggest that this type of approach could also work against the abuse of other substances. In another animal study, a Mayo Clinic team tested gene therapy to alleviate cocaine addiction. In this case, the scientists modified the production of the BChE protein, which breaks down cocaine for absorption. Several studies have shown that injection of the CocH protein breaks down cocaine much faster, before the user even feels the high associated with the drug. That makes it easy to cut back or stop altogether, but this requires regular injections. Researchers at the Mayo Clinic in Rochester, Minnesota verified that it’s possible to introduce the gene that produces the CocH protein into the liver through adeno-associated viruses, similar to those used for the treatment of alcoholism.

In the test — which was conducted on mice — it was observed that the animals taking cocaine became hyperactive and experienced liver damage. However, those who received the gene therapy continued to behave normally and didn’t show liver damage, because their CocH proteins absorbed the drug before it took effect. This suggests that it may be useful to reduce the effect of this substance in addicts, who would be protected from a serious relapse if they tried it again.

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