Gene Therapy Offers New Way to Fight Alcohol Use Disorder

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Aug. 21, 2023 – A type of gene therapy that reboots the brain’s reward system could curb drinking in those with severe alcohol use disorder.

Researchers from Oregon Health & Science University implanted the therapy directly into the brains of rhesus monkeys that had been conditioned to drink eight to 10 alcoholic drinks a day. A harmless virus that carried a specific gene was placed in the region of the brain that regulates dopamine, which provides feelings of reward and pleasure.. 

“We wanted to see if we could normalize the dopamine in these motivational areas – if, indeed, motivation to overdrink or drink heavily would be mitigated,” said study author Kathleen Grant, PhD, a professor and chief of the Division of Neuroscience at the university’s Oregon National Primate Research Center.

The need for new alcohol use disorder treatments may be more dire than ever. Alcohol-related deaths in the United States increased dramatically between 2007 and 2020, especially in women, according to research published in the journal JAMA Network OpenThe next year, they spiked again, to 108,791 alcohol-related deaths in 2021 alone, according to the National Institutes of Health. That’s slightly more than the number of drug overdoses recorded in 2021.

For the 29.5 million Americans with alcohol use disorder, also known as alcohol abuse or dependence, the road to recovery can be challenging. One reason is that the reward systems in their brains are working against them. 

At the first taste of alcohol, your body releases the feel-good brain chemical dopamine. But if you drink too much for too long, your brain reduces dopamine production, and you want even more alcohol to feel good again.

The gene researchers placed in the monkeys’ brains is called glial derived neurotrophic factor. It is a “growth factor,” meaning it stimulates cells to multiply. It may help improve function of brain cells that synthesize dopamine, effectively resetting the whole system and reducing the urge to drink. 

The study was surprisingly successful. Compared to primates that received a placebo IV, those that received the growth factor gene decreased their drinking by about 90%. They basically quit drinking, while the primates that got the placebo resumed their habit. 

A similar procedure is already used in patients with Parkinson’s disease. But more animal studies, and human clinical trials, would be needed before this therapy could be used in humans with alcohol use disorder. This invasive treatment involves brain surgery, which has risks, so it would likely be reserved for those with the most severe, dangerous drinking habits.

“I think it’d be appropriate for individuals where other treatment modalities just weren’t effective, and they’re worried for their lives,” Grant said.

Alcohol Use Disorder Treatments

Today, treatment for alcohol use disorder ranges from a brief conversation with a health care provider, in mild cases, to psychiatric treatment or medication in moderate or severe cases.

There are four FDA-approved treatments for alcohol use disorder and a few more medications that health care providers can prescribe off-label.

“They’re not widely used,” said Henry Kranzler, MD, a professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania Perelman School of Medicine. “They’re shockingly underutilized.”

One reason: Just 4.6% of people with alcohol use disorder seek treatment each year, according to NIH data

“Some of the issues include the ubiquity of alcohol, and its acceptance in American culture – and the fact that that makes it difficult for people to acknowledge that they have a problem with alcohol,” said Kranzler.

But another problem is that many health care professionals don’t recognize and treat alcohol use disorder in patients who do seek care. Those seeking treatment for alcohol use disorder can find a qualified provider at the American Academy of Addiction Psychiatry or American Society of Addiction Medicine directories.

The Future of Treatment

Ongoing research could lead to more treatments, and make them more available and more appealing.

Unlike many other drugs that work on a single receptor in the body – like opioids that target opioid receptors, or nicotine, which targets choline receptors – alcohol affects many different receptors, said Robert Swift, MD, PhD, a professor of psychiatry and human behavior at Brown University Alpert Medical School. It also penetrates cells at high doses.

“There are so many different effects of alcohol, which makes it very hard to treat,” he said. “But on the other hand, it gives us an advantage, and there are probably different points that we can attack.”

Other exciting developments are underway, although more research, including clinical trials in humans, is needed before they arrive.

Some of the most promising:

  • Hallucinogens. In the 1950s, before they became illegal, these trippy drugs helped people drink less. Even Bill Wilson, co-founder of Alcoholics Anonymous, used hallucinogenic treatment in his recovery; it helped him envision overcoming a challenge. Today, there is renewed interest in hallucinogens for alcohol use disorder. In a study published in JAMA Psychiatry, people with alcohol use disorder who were given the hallucinogen psilocybin along with therapy spent fewer days drinking heavily over the following 32 weeks than people who received a different medication. Don’t try to do this yourself, though. “It’s not just taking a hallucinogen and having a trip,” Swift said. “It’s a therapy-guided session, so it’s a combination of using the hallucinogenic substance with a skilled therapist, and sometimes two skilled therapists, helping to guide the experience.”
  • Epigenetic editing. Alcohol exposure can affect the activity of a gene in your amygdala, a brain region involved in emotional processing. Researchers at the University of Illinois at Chicago found that by editing that gene in rats through an IV of genetic material, they reduced the rodents’ drinking and anxiety. 
  • Oxytocin. The so-called love hormone, produced by your brain when you hug your partner, could help reset the dopamine system to make alcohol less appealing. “There are oxytocin receptors on dopamine neurons, and oxytocin makes your dopamine system more effective,” Swift said. In a recent study from the Medical University of South Carolina, mice injected with oxytocin didn’t drink during a stressful situation that could have otherwise led to relapse.
  • Ghrelin. This stomach hormone that helps you stay full could help curb drinking. In a study published in Neuropharmacology, mice that received drugs that increased ghrelin reduced their alcohol intake.