Alcohol consumption is associated with many health problems and it is estimated that more than two million people die every year in the world because of it. This week the magazine nature medicine presents 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 to insert into the patient’s cells the instructions to produce proteins that correct a certain problem. It is already used to treat some types of cancer, hemophilia, rare diseases and even Parkinson’s. Now, a group of scientists from the Oregon Health and Science University (USA) has tested a gene therapy, which is already used against this neurological disease, to measure its potential 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 therapeutic options for this condition is the insertion of the growth factor GDNF into the brain with surgery and 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 that behavior. However, chronic alcohol consumption causes the brain to get used to it and stop generating dopamine, something that also kills the pleasant sensation of drinking. The study authors, led by Kathleen Grant, director of the division of neuroscience at Oregon National Primate Research Centerproposed that restoring the balance in dopamine production would serve to reduce alcohol consumption and tested their hypothesis in monkeys.
The experiment was carried out with eight macaques that had been given a large amount of ethanol diluted in water to generate alcoholism. Later, four of them received treatment with gene therapy and 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 and 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,” Grant celebrates.
an expensive therapy
The road to treat people with alcohol addiction with this system will still be long. On the one hand, this type of treatment is usually very expensive and would only be applied when other more conventional strategies fail. In addition, this system requires surgery, something that does not facilitate its widespread application either. Finally, the authors warn of possible limitations, such as the possibility of generating problems due to an excess of dopamine in the brain of the subjects. “Although 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 the growth factor GDNF in the same region of the brain treated in this experiment increased the chances of relapse in models of cocaine addiction.
Those responsible for the study suggest that this type of approach could also work against the abuse of other substances. at another job developed with animals, a team from the Mayo Clinic 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 requires regular injections. Researchers at the Mayo Clinic in Rochester, Minnesota (USA) verified that it was 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 on mice, animals taking cocaine were seen to become hyperactive and have liver damage. However, those who had received the gene therapy continued to behave normally and did not 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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