According to data from the World Health Organization According to the WHO (WHO), alcoholism “is a causal factor in more than 200 diseases and disorders.” Among them, alcohol abuse can impact mental health by worsening existing conditions such as depression or lead to new problems such as severe memory loss, anxiety and, again, depression.
In this context, recently, the journal Nature Medicine presented a novel approach to treat the most serious cases of addiction to this substance: gene therapy.
The authors of the study, led by Kathleen Grant, director of the division of neuroscience at the Oregon National Primate Research Center, claimed that restoring balance in dopamine production would serve to reduce alcohol consumption and tested their hypothesis in monkeys.
Treatments based on this therapy use harmless viruses as vehicles to insert into the patient’s cells the instructions to produce proteins that correct a certain problem.
It is now used to treat Parkinson’s disease, some cancers, hemophilia and rare diseases. Now, a group of scientists from the Oregon Health and Science University (USA) tested gene therapy, which is already used against this neurological disease, to study its possibility of treatment against alcoholism.
In the case of Parkinson’s disease, the neurons that produce dopamine They begin to die. Dopamine is a neurotransmitter with several functions associated with motivation and pleasure. Without this substance, the body loses control of movement and symptoms Best known of the disease: tremors, slowness in movements, deterioration of posture and balance, changes in speech and writing.
One of the therapeutic options for this disease is the insertion of GDNF growth factor 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 brain get used to it and stop generating dopamine, something that also ends the pleasurable sensation of drinking. The researchers said restoring balance in dopamine production would be helpful in reducing alcohol consumption.
“These preclinical findings suggest that gene therapy aimed at preventing relapse may be a possible Therapeutic strategy for alcohol use disorder,” the scientists said.
The research was conducted with eight Macaques who had been given a large amount of ethanol diluted in water to produce alcoholism. Then, four of them received the gene therapy treatment and the other four were given only a placebo.
In the four animals that received the growth factor GDNF, dopamine regained balance in their brains and reduced 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 said.
“GDNF expression eliminated the return to drinking behavior during a 12-month period of repeated alcohol withdrawal and reintroduction challenges,” they explained in the published study.
However, the researchers cautioned that The road to treating people with alcoholism through gene therapy will still be long. On the one hand, these types of treatments are usually very expensive and would only be applied when other strategies do not work. In addition, this system requires surgery, something that does not facilitate its application in a generalized way.
In addition, the authors warn of possible limitations, such as the possibility of generating problems due to a Excess dopamine in the brain of the subjects. “Although beneficial in the context of excessive alcohol consumption, Increased dopamine can be detrimental to other behaviors such as stimulant use disorders.” Previous studies have shown that an overexpression of GDNF growth factor in the same brain region treated in this experiment increased the odds of relapse in models of cocaine addiction.
The authors of the study suggested that this type of approach could also work against the abuse of other substances. In other work carried out with animals, a team from the Mayo Clinic in Rochester, Minnesota (USA), studied gene therapy in cases of cocaine addiction. In this case, the researchers modified the production of the BChE protein, which breaks down cocaine for absorption.
Several studies have shown that injecting the CocH protein breaks down cocaine much faster, before the user even feels the pleasure associated with the drug. That makes it easier to reduce your intake or avoid it altogether, but it requires regular injections.
The researchers of the Mayo Clinic They found 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 showed no 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.
“These results indicate that a transfer of the AAV8-hCocH gene to the liver at reasonable doses is safe, well-tolerated and effective. Therefore, gene transfer therapy emerges as a radically new approach to treating compulsive cocaine abuse,” they said in the study.
