Alcohol use disorder (AUD), commonly known as alcoholism, affects millions of people. While medications and treatments exist for AUD, relapse is common. Partially to blame are the neurological effects of alcoholism: chronic drinking impairs dopamine signaling in a part of the brain called the mesolimbic system, also known as the reward pathway. Previous research showed that stimulation of this pathway in mice causes less alcohol consumption. In a recently published study, a group of researchers have used this information to test a gene therapy for AUD in monkeys.
These researchers modeled AUD in rhesus macaque monkeys by exposing them to high levels of alcohol over a few months, followed by six months where they could choose between alcohol and water. During those six months, the amount the monkeys drank mimicked binge drinking in humans. In four of the animals, the scientists then delivered a gene therapy to specific neurons in the mesolimbic system. The added gene permanently increased the activity of the GDNF protein, which regulates dopamine in neurons. The other four monkeys did not receive the therapy. For the next year, the monkeys went through alternating month-long periods where they either had or did not have alcohol available. Monkeys that received the treatment drank much less alcohol and took much more time to start drinking in each period. The reward pathway of the treated monkeys also had a significant jump in dopamine activity, meaning that the treatment likely restored the natural function.
Having a successful treatment for alcoholism in non-human primates is a major breakthrough. Still, this research is just a proof-of-concept, and the researchers say that the therapy needs a lot more testing, especially to look at its effect on drugs other than alcohol. Nonetheless, gene therapy represents an exciting move forward for the treatment of alcoholism and other drug use disorders.
This study was led by Matthew M. Ford, a Visiting Associate Professor of Psychology at Reed College, Brianna George, a Postdoctoral Fellow at the University of North Carolina Chapel Hill, Victor S. Van Laar, a Research Scientist at the Ohio State University, and Katherine Holleran, an Instructor in Physiology and Pharmacology at Wake Forest University.
Managing Correspondent: Alex Yenkin
Press Article: “Study shows promise of gene therapy for alcohol use disorder,” OHSU News
Original Article: “GDNF gene therapy for alcohol use disorder in male non-human primates,” Nature Medicine
Image Credit: Pxfuel