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AUD Research Continues at Scripps

HEALTH: $10M Alcohol Use Disorder Grant Renewed

For the last 45 years, scientists at Scripps Research have studied the biology behind alcohol use disorder (AUD) – a disease that afflicts an estimated 29.5 million people in the U.S. Thanks to a $10 million grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), that research will continue for at least another five years.

The grant will fund The Scripps Research Alcohol Research Center (TSRI-ARC) for five years, carrying the research into its 50th year of consecutive NIAAA funding – first beginning in 1977.

Barbara Mason, Ph.D.
Director
The Scripps Research Alcohol Research Center

“A lot of exciting things have happened in the AUD field over the last 45 years, and the center has been at the forefront of many of them,” said TSRI-ARC Director Barbara Mason, Ph.D., the Pearson Family chair and director of the Pearson Center For Alcoholism and Addiction Research at Scripps Research.

Mason added that NIAAA funding of alcohol research center is a competitive process, involving review and scoring by a panel of scientists in the field every five years.

“We are one of the last two remaining original alcohol research centers since the inception of NIAAA’s alcohol research center program, which was initiated by congressional mandate,” she said.

The grant will fund five separate research components to better understand the biology of AUD, including molecular research, led by associate professor Candice Contet, Ph.D.; functional connectomics, led by associate professor Olivier George, Ph.D.; neurochemistry, led by associate professor Rémi Martin-Fardon, Ph.D.; neurophysiology, led by Vice Chair Marisa Roberto, Ph.D.;  and neurocurcuitry, led by associate professor Eric Zorrilla, Ph.D.

Senior Scientific Director Amanda Roberts, Ph.D. will provide animal models and professor John Yates III, Ph.D. will provide neuroproteomics resources for the research.

The grant also includes funding for high school and college internships for students in high-risk, underserved communities to further interest AUD research. The projects funded by the grant include researchers not only at Scripps Research, but also collaborators at the University of California, San Diego.

Advances in Treatments for Alcoholism

Over the course of 45 years of NIAAA funding, TSRI-ARC researchers have shown the importance of changes in brain neurocircuits as drivers of alcohol misuse and addiction.

“People used to think that alcohol use disorder was really an indication of flawed willpower,” Mason said. “Our work here at Scripps Research over the years has gone a long way in changing that perception by identifying the neurocircuits and molecules that are involved in driving this disorder.”

Recent developments in TSRI-ARC’s research include a shift from focusing on treatments that target reducing acohol’s “rewarding effects” to a focus on long -term recovery by “normalizing the activity of brain systems involved in driving the stress response of not drinking,” Mason said. “The neuroinflammation associated with chronic heavy drinking interacts with the brain stress systems and are viable targets in reversing the stress of not drinking.”

TRSI-ARC researcher also recently published a study showing the anti-imflammatory drug apremilast, used to treat the skin condition psoriasis, “significantly reduced drinking by about half in individuals with severe AUD,” Mason said.

Previous research at TRSI-ARC showed how brain signaling molecules play a role in AUD, which led to clinical trials on drugs targeting this system. In 2014, Mason led a trial on the epilepsy drug gabapentin in treating AUD that led to the inclusion of of the drug in new practice guidelines for AUD treatment.

“The American Psychiatric Association has published a guideline for pharmacological treatment of AUD that includes prescribing gabapentin for patients who have a goal of decreasing or quitting drinking,” Mason said, adding that gabapentin is “particularly beneficial” in helping patients with sleep disturbances associated with “acute and protracted withdrawal.”

Next Areas of Research

With the NIAAA grant renewal, TRSI-ARC researchers will expand their focus to include a set of cellular and molecular mechanisms in the brain that normally limit compulsive behavior. The research team wants to know what happens to impair these executive function control mechanisms in people with AUD. They hypothesize that impairment of these mechanisms make people more susceptible to developing AUD.

Mason said TRSI-ARC hopes to capitalize on these new focus areas and capitalize on drug treatments identified by the basic science. However, she pointed out, getting these drugs to people afflicted with AUD will require moe than just research.

“There is an abundance of drug targets for AUD. A challenge involves engaging the interest of the pharmaceutical industry in developing the drugs commercially so that they are granted FDA approval and become available to treat AUD,” she said, adding that it has been “about 20 years since the last new drug was commercially developed and FDA-approved for the treatment of AUD in the U.S.”

Scripps Research

Founded: 1924
CEO: Peter Schultz
Business: Medical and scientific research institute
Headquarters: La Jolla
Employees: 2,400+
Revenue: Over $320 million (2020)
Website: scripps.edu
Notable: The Scripps Research Alcohol Center in one of only two original alcohol centers still operating since the National Institute on Alcohol Abuse and Alcoholism research program was initiated by congress.

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