A new study from researchers at the University of Kentucky's Sanders-Brown Center on Aging is exploring whether a drug originally developed to combat neuroinflammation in dementia could also help reduce the harmful brain inflammation associated with alcohol withdrawal - a discovery that could eventually open new treatment pathways for alcohol use disorder.
The study recently published in the journal Alcohol, examines the anti-inflammatory effects of the experimental compound MW150 during acute alcohol exposure and withdrawal in animal models. Researchers found the drug significantly reduced select inflammatory markers, particularly during alcohol withdrawal.
The work was led by researchers in the laboratory of Linda Van Eldik, Ph.D., director of the Sanders-Brown Center on Aging and a nationally recognized leader in neuroinflammation research. Van Eldik's laboratory has spent years developing small-molecule therapeutics targeting inflammation pathways linked to neurodegenerative diseases, including Alzheimer's disease.
"Our findings provide an important early step toward understanding whether compounds like MW150 could be repurposed to address neuroinflammation tied to alcohol withdrawal," said Caleb Bailey, Ph.D., co-author of the study and a researcher in Van Eldik's lab. "Alcohol use disorder is incredibly difficult to treat because relapse rates remain so high, especially during withdrawal. We wanted to explore whether reducing inflammation in the brain could potentially lessen some of those effects."
The study focused on p38α MAPK, a signaling pathway strongly associated with inflammation in the brain. Researchers tested MW150 in two different central nervous system cell culture models and observed reductions in inflammatory responses during withdrawal periods.
Although the research remains in its earliest stages, the findings are particularly noteworthy because MW150 - along with a related drug Neflamapimod - is already being studied in clinical trials for dementia and other neurodegenerative conditions.
"That gives this work added significance," Bailey said. "Because these compounds are already further along in development for other neurological diseases, it raises the possibility that they could someday be repurposed more efficiently for alcohol-related conditions if future studies continue to show promise."
According to the researchers, alcohol withdrawal can trigger neuroinflammation that contributes to chronic relapse and long-term neurological damage. Kentucky continues to face growing concerns surrounding alcohol use disorder, making the search for new therapeutic strategies especially relevant for the Commonwealth.
"It's no secret that bourbon and alcohol are deeply tied to Kentucky culture," Bailey said. "But at the same time, we can't ignore the very real public health burden of alcohol use disorder across the state. Even if this approach does not ultimately change alcohol use behaviors directly, reducing neuroinflammation could still have important neuroprotective effects that improve patient outcomes."
The project also marked a major milestone for undergraduate researcher McKenna Green, who served as first author on the publication - her first lead-author paper.
Green, who was also a Lewis Honors College student, recently graduated with dual degrees in psychology and public health. Originally from Cadiz, Kentucky, she joined Van Eldik's lab in 2023 and has been accepted into UK's Cognitive Neuroscience Experimental Psychology doctoral program.
"This publication represents years of mentorship and hands-on training in the lab," Green said. "Being able to contribute to research that could someday help people struggling with alcohol use disorder has been incredibly meaningful."
Researchers emphasized that much more work remains before the findings could translate into clinical applications. Future studies will evaluate whether MW150 produces similar anti-inflammatory effects in living animal models and whether those effects influence alcohol relapse behaviors.
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number T32AG078110 and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number T32AA027488. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
