Researchers see promise in gene therapy for chronic drinkers

NEW YORK, Aug. 14 (UPI) -- A form of gene therapy used to treat Parkinson's disease may significantly reduce alcohol use among chronic heavy drinkers, a new study suggests.

Results of the study, conducted as a clinical trial in nonhuman primates, were published Monday in the journal Nature Medicine.

Researchers demonstrated that implanting a specific type of molecule that induces cell growth effectively resets the brain's dopamine reward pathway in animals predisposed to heavy alcohol consumption.

Dopamine -- a chemical released in the brain -- is associated with feeling pleasure.

The gene therapy procedure, which involves brain surgery, may help in the most severe cases of alcohol use disorder.

"This treatment was incredibly effective," the study's co-senior author, Kathleen Grant, told UPI via email. "The treated monkeys' drinking went down to almost zero."

Grant is a professor and chief of the neuroscience division in the Oregon Primate National Research Center at Oregon Health & Science University in Portland.

"For months on end, these animals would choose to drink water and just avoid drinking alcohol altogether," Grant said. "They decreased their drinking to the point that it was so low we didn't record a blood-alcohol level.

"This could potentially be a lifesaving tool for the most severe cases of alcohol use disorder that do not respond to other treatments."

The implanted virus, which is not harmful, carries a gene that codes for the protein known as glial-derived neurotrophic factor, or GDNF.

It was injected in a specific area of the brain of rhesus macaque monkeys that voluntarily and heavily drink ethanol diluted in water. After four macaques underwent the procedure, their consumption dropped by more than 90% compared with a control group.

"The monkeys that were treated with this gene permanently started overexpressing dopamine and they decreased their drinking substantially," Grant said.

Alcohol use disorder and alcohol-related deaths remain a major problem in the United States and around the world. An estimated 140,000 fatalities occur annually from alcohol-related causes, according to the National Institute on Alcohol Abuse and Alcoholism.

According to the World Heart Federation, in 2019, nearly 2.4 million deaths were attributed to alcohol, accounting for 4.3% of all deaths globally. Alcohol also has been linked to a variety of diseases and cancer.

An estimated 12% of all alcohol consumers meet the criteria for alcohol use disorder. Yet, few pharmacotherapies are approved by the U.S. Food and Drug Administration, and fewer than 20% of affected individuals seek treatment in part because of the social stigma associated with alcohol use, Victor Van Laar, co-first author of the new study, told UPI via email.

Van Laar is a research scientist with the department of neurological surgery at Ohio State University's Wexner Medical Center and College of Medicine in Columbus.

Current treatments for alcohol use disorder "are typically a combination of social or psychological intervention with oral medications intended to make the act of imbibing alcohol less pleasurable or even nauseating," Van Laar said, adding that "continued adherence to social programs or to the medications is a frequent problem."

He noted that as many as 90% of patients with alcohol use disorder "report a return to drinking alcohol within four years of beginning these treatments."

The most common drugs used to treat, but not cure, alcohol use disorder are acamprosate, disulfiram and naltrexone, according to the Substance Abuse and Mental Health Services Administration, part of the U.S. Department of Health and Human Services.

"This new study describes a form of treatment that permanently alters the brain through surgery, so the therapy would be limited to those with the most severe forms of alcohol use disorder," Grant said.

"It would be most appropriate for people who have already shown that all our normal therapeutic approaches do not work for them. They are likely to create severe harm or kill themselves or others due to their drinking."

She added that this gene therapy procedure is already used in clinical trials for adults with Parkinson's disease and in children with a rare genetic disorder known as aromatic L-amino acid decarboxylase deficiency that, among other symptoms, causes difficulty with movement.

"Additional studies are needed to determine whether this can be a recommended treatment for severe alcohol use disorder in humans," Grant said.

Alcohol use is a leading risk factor for death worldwide. "When considering both personal and societal harms, it may be one of the most harmful substances that people use. In the U.S., around 3 in 10 adults use alcohol in an unhealthy manner," Dr. Steven Tate, who was not involved in the study, told UPI via email.

Tate is a clinical assistant professor specializing in addiction medicine within the department of psychiatry and behavioral sciences at Stanford University School of Medicine in Palo Alto, Calif.

"All three FDA-approved medications [for alcohol use disorder] are criminally underused," Tate said. "Some estimates suggest only about 8% of individuals who meet criteria for alcohol use disorder are prescribed them."

"The idea of gene therapy for alcohol use disorder is fascinating, and I am glad people are doing this research," he said. "It's hard for me to be too excited about this new cutting-edge treatment, however, when we can't even get the cheap medications we know work to the patients who need them."

Dr. Kenneth Zoucha, who was not involved in the study, told UPI via email that this research brings hope to those who are suffering as they discontinue the excessive alcohol intake, which may have caused physical, emotional, psychological and spiritual damage to them, their family and friends.

Zoucha is director of addiction medicine for the department of psychiatry at the University of Nebraska Medical Center in Omaha.

While this study in rhesus monkeys raises concerns of human applicability, Zoucha said that medicine already has established the value of gene therapy for other disorders of the central nervous system.

"We must never give up hope that one day, we will continue to find effective treatments for those suffering from addiction," he said.