Gene therapy offers hope for severe alcohol addiction, study finds

Research conducted in the United States on the release of dopamine revealed that, after going through the treatment, the monkeys reduced their consumption by up to 90%.

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Dependence manifests itself through an uncontrollable desire to ingest alcohol and a difficulty in controlling consumption - Photo Reproduction / Internet

Alcohol dependence is a global health problem that affects millions of people, harming both the physical and mental health of individuals and their interpersonal relationships. However, a promising new study points to a possible breakthrough in treating this debilitating condition through gene therapy that is currently in the testing phase in individuals with Parkinson's disease and may represent a unique approach in the treatment of severe alcohol dependence.

The Alcohol Addiction Challenge

Addiction is characterized by a compulsive craving for alcohol and difficulty controlling drinking, despite the negative consequences for health and personal life. It is influenced by a complex combination of genetic, environmental and neurobiological factors, which makes it a difficult condition to treat. The abuse of alcohol constitutes the main risk element for deaths, disabilities and health issues among individuals aged 15 to 49 years. Data released in February this year by the World Health Organization (WHO) indicated that excessive and abusive consumption of alcohol is the cause of 2.8 million deaths per year in the world.

Study

Research carried out on monkeys with a predisposition to excessive alcohol consumption revealed a drastic reduction in consumption after the intervention. Professor Kathleen Grant, co-leader of the study and linked to the National Primate Research Center at the Oregon Health Sciences University in Beaverton, USA, reported that alcohol consumption was virtually eliminated. For consecutive months, these animals chose to drink water, demonstrating a clear aversion to alcohol.

Similar to other addictive substances, alcohol triggers the release of dopamine, a chemical compound linked to well-being, in the brain. However, prolonged consumption reduced this dopamine release, resulting in a decrease in pleasure associated with drinking. Consequently, people with alcohol dependence often seek to increase consumption to sustain a drunken state.

"It seems like they're drinking more because they feel the need to maintain a drunken state," Grant said.

The idea of ​​gene therapy seeks to restructure the dopamine reward system, amplifying the activity of the air cells responsible for the synthesis of this substance. Similar to humans, certain apes are more predisposed to consuming large amounts of alcohol than others. When presented with an alternative solution containing 5% alcohol, equivalent in strength to beer, along with their usual sources of food and water, it is observed that some monkeys tend to consistently choose alcohol.

Grant and the other members of his team asked about the possibility of decreasing cravings for alcohol consumption by resetting dopamine reward circuits. To achieve this goal, they used a harmless virus to introduce the gene coding for a protein called neurotrophic factor glial-derived (GDNF) in a brain region associated with addiction and the feeling of reward.

"We targeted the dopamine-producing cell bodies with this gene to increase dopamine synthesis, replenishing or restoring what chronic consumption took away," Grant said.

Four primates with alcohol dependence were subjected to the experiment, which used magnetic resonance imaging to precisely direct the administration of the substance to the right location. A similar approach is currently being tested in adults with Parkinson's and children with an unusual genetic condition called aromatic L-amino acid decarboxylase deficiency. This condition affects the nervous system and results in motor difficulties.

Results

The study, published in the journal Nature Medicine, revealed that the monkeys began to continuously express dopamine at high levels due to the activation of the GNDF gene. This resulted in a Significant reduction of up to 90% in subsequent alcohol consumption. On the other hand, the monkeys that received an inactive variant of the gene maintained their drinking patterns. The researcher explained that in animals that received GNDF therapy, there was an inhibition of dopamine levels, leading them to consume only one to two drinks a day, compared to the previous eight to 10 drinks.

"We are entering an era of gene therapy for neurological disorders and perhaps psychiatric disorders, and I think this study is very promising in that direction," said the researcher.

Grant emphasized that animal studies are needed before the technique can be tested in humans. Furthermore, given that the gene therapy procedure involves surgical intervention in the brain and is irreversible, it is certain that it should only be used in more severe cases of alcohol dependence. Grant stressed that this approach would be most appropriate for individuals in whom all other therapeutic modalities have been ineffective. She reinforced that the option for an invasive and irreversible therapy should only be considered when someone's life is really at risk.