Genetic Analysis Identifies Possible Acamprosate Biomarker

Researchers at the Mayo Clinic have identified a potential biomarker to identify people who would most benefit from acamprosate treatment for alcoholism.

The biomarker is a variant of a gene called GRIN2B, and while it’s not the first gene to be tied to sobriety medications like acamprosate or naltrexone, it’s the first one that has been verified in two independent study groups—a key step if this gene eventually will be used to help guide treatments.

In this study, which was published in the November Translational Psychiatry, researchers enrolled 225 alcohol-dependent subjects participating in a residential or outpatient sobriety program associated with the Mayo Clinic and gave them acamprosate to supplement their regular regimen. The participants’ sobriety was reassessed after three months, and abstinence duration was matched with genetic data.

Among the numerous candidate genes analyzed, GRIN2B—which encodes a portion of the N-methyl-D-aspartate (NMDA) receptor—showed the strongest correlation with longer abstinence. While the NMDA receptor is principally involved in learning and memory, it is also implicated in many aspects of alcohol abuse, including dependence, cravings, and risk of relapse. Acamprosate is thought to help reduce alcohol cravings in part by interacting with the NMDA receptor

While the biological aspects of this common gene variant—it was found in almost half of the study participants—are intriguing, lead study author Victor Karpyak, M.D., Ph.D., an assistant professor in the Department of Psychiatry and Psychology at the Mayo Clinic, believes the screening value holds great promise.

“The patients we enrolled in this trial came from various community-based programs that reflect the broad spectrum of alcohol treatment options available in the United States,” he told Psychiatric News. “These programs are everywhere, so there are many people who could benefit if we can identify potential responders. Right now, only 10 percent of people who enroll in an alcohol treatment program will end up using medications as part of their regimen.”

The clinical utility of GRIN2B passed an important hurdle when researchers in Germany confirmed a connection between the GRIN2B variant and longer abstinence in a second group of 110 men seeking alcohol treatment, though Karpyak did caution that additional validation is still needed.

“Importantly, because we did not have a placebo arm in our study, we cannot say for sure if this particular marker is associated with acamprosate or another biological factor that influences sobriety,” he said, adding that his research group is planning a follow-up study that will be blinded and placebo-controlled to resolve this issue.

He also noted that the long-term value of acamprosate therapy in people with this variant is still an unknown, but the first three months of treatment represent a critical juncture for people with alcohol problems, and the longer someone can stay sober in the short term, the better the probability of sustained sobriety.

This work was supported by grants from the National Institutes of Health, Mayo Clinic, and the German Federal Ministry of Education and Research. Forest Pharmaceuticals provided the acamprosate but otherwise had no involvement in the study. ■