October 3, 2023

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Gene Therapy Using AAV Shows Long-Term Efficacy in Treating Alcoholism

Gene Therapy Using AAV Shows Long-Term Efficacy in Treating Alcoholism



 

Gene Therapy Using AAV Shows Long-Term Efficacy in Treating Alcoholism

Alcohol consumption’s detrimental effects on health are widely recognized, with numerous studies highlighting its link to cancer and various other diseases, including addiction.

In August 2018, a significant study published in The Lancet, a leading medical journal, revealed that alcohol is a major risk factor for disease and premature death among individuals aged 15 to 49 globally.

Nearly one-tenth of global deaths were attributed to alcohol consumption [1].

 

Global statistics indicate that nearly 300 million people suffer from Alcohol Use Disorder (AUD), often characterized by cycles of relapse even after attempted abstinence, even when using FDA-approved medications for addiction treatment.

 

On August 14, 2023, researchers from Ohio State University, Oregon Health and Science University, Wake Forest University School of Medicine, and the University of California, San Francisco, published a research paper titled “GDNF gene therapy for alcohol use disorder in male non-human primates” in the prestigious medical journal Nature Medicine [2].

The study, conducted on non-human primates (rhesus macaques), demonstrated that delivering human Glial Cell-Derived Neurotrophic Factor (hGDNF) to the Ventral Tegmental Area (VTA) of the midbrain using Adeno-Associated Virus type 2 (AAV2) significantly reduced alcohol consumption and prevented relapse in alcohol-seeking behavior after cessation.

 

Gene Therapy Using AAV Shows Long-Term Efficacy in Treating Alcoholism

 

 

Professor Krystof Bankiewicz, the lead author of the study, emphasized that this gene therapy targets alterations in dopamine function within the midbrain’s reward pathway caused by prolonged alcohol consumption.

Experimental results indicated that this approach could prevent relapse in alcohol-seeking behavior post-abstinence, potentially offering a sustained, one-time treatment for severe alcohol addiction, also known as AUD.

 

Gene Therapy Using AAV Shows Long-Term Efficacy in Treating Alcoholism

 

Excessive alcohol consumption alters dopamine release in the Ventral Tegmental Area (VTA) neurons of the brain’s reward pathway.

As AUD progresses, these changes become more pronounced, including decreased dopamine release, reduced dopamine receptor sensitivity, and increased dopamine reuptake.

These alterations result in dopamine levels in the pathway falling below normal levels, creating a “hypodopaminergic” state that drives individuals to resume alcohol consumption after a period of abstinence. Currently, no treatment or medication specifically targets this pathway.

 

In this study, researchers administered AAV2 carrying the human Glial Cell-Derived Neurotrophic Factor (hGDNF) to the VTA of eight rhesus macaques, while four other macaques received sterile saline as a control.

These macaques were accustomed to consuming 4% alcohol before treatment. The treatment group exhibited sustained expression of hGDNF in the brain, and during the subsequent 12 months, they demonstrated no relapse in alcohol consumption during periods of repeated abstinence-alcohol reintroduction challenges.

This behavioral change was accompanied by neurophysiological adjustments in the ventral striatum’s dopamine signaling, countering the hypodopaminergic state associated with chronic alcohol use.

This suggests that GDNF gene therapy targeting the VTA could potentially reduce alcohol consumption and prevent relapse, offering a promising strategy for treating AUD.

 

 

 

 

Paper Links:
1. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31310-2/fulltext
2. https://www.nature.com/articles/s41591-023-02463-9

Gene Therapy Using AAV Shows Long-Term Efficacy in Treating Alcoholism

(source:internet, reference only)


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