# PHARMACOGENOMICS OF ACAMPROSATE TREATMENT OUTCOME

> **NIH NIH U01** · MAYO CLINIC ROCHESTER · 2020 · $719,820

## Abstract

The economic and health consequences of Alcohol Use Disorders (AUDs) call for efficient treatment
strategies. The discovery of response biomarkers is expected to improve treatment outcomes by allowing for
the personalization of treatment selection. Our preliminary findings indicated an association of sobriety in
acamprosate-treated alcoholics with a polymorphism in the GRIN2B gene and changes in plasma glutamate
levels. Our neuroimaging data indicate an association of glutamate levels in the left dorsolateral prefrontal
cortex with alcohol cravings and decreased glutamate levels in the anterior cingulate in response to
acamprosate treatment. Yet, previous studies used a limited set of candidate genes and did not include a
placebo control for the determination of the acamprosate-specific effects. Moreover, no studies have yet
assessed the genetic contribution to sobriety vs. other treatment outcomes. Therefore, Project 1 will search
for genetic markers associated with acamprosate vs. placebo treatment response in AUD patients on a
genome-wide scale in the combined sample including alcoholics treated by acamprosate and placebo in the
COMBINE, PREDICT and P20 CITA studies and a new sample of 800 AUD patients treated in community-
based programs in a double blind randomized placebo controlled study of acamprosate. This will allow us to
perform a meta-analyses of genome-wide association with AUD treatment outcomes in the largest combined
sample used for pharmacogenomic studies in the field of alcoholism research (total N>2400). We will also
assess the heritability explained by common polymorphisms and the genetic architecture for different
measures of alcoholism treatment response. Finally, we will conduct pharmacometabolomic- and
pharmacoimaging-guided pharmacogenetic study by selecting candidate targets for additional analyses in
pathways related to metabolic and imaging markers associated with acamprosate response in Projects 2 and
3. We also use functional analyses in the neuronal-derived iPS cell lines described in Project 2 for functional
validation of our findings.
RELEVANCE (See instructions):
Completion of these studies will provide evidence leading to individualized treatment selection for AUD
patients and guide development of treatment strategies based on the biomarkers of response.

## Key facts

- **NIH application ID:** 10000815
- **Project number:** 5U01AA027487-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Joanna M Biernacka
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $719,820
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000815

## Citation

> US National Institutes of Health, RePORTER application 10000815, PHARMACOGENOMICS OF ACAMPROSATE TREATMENT OUTCOME (5U01AA027487-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000815. Licensed CC0.

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