# Alcohol Use Disorder:  Acamprosate Pharmacometabolomics-informed Pharmacogenomics

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $604,737

## Abstract

Alcohol use disorder (AUD) represents a major medical and social burden worldwide and results in immense
suffering for AUD patients and their families. A major goal of AUD research is the development and
optimization of the use of effective drugs to treat this disorder. However, only a very small number of drugs—
acamprosate, naltrexone and disulfiram—have received FDA approval for the treatment of AUD in the United
States, and only a small proportion of alcoholic patients respond to treatment with these agents by achieving
sustained abstinence. It would be a major achievement for Precision Medicine if we were to develop ways to
better individualize the drug therapy of AUD patients in order to increase the frequency of the achievement of
abstinence and to select the patients most likely to respond prior to the initiation of drug therapy. The studies
of acamprosate proposed in this application will help to move us toward those goals and—by using
acamprosate both as an approved therapeutic agent and as a “molecular probe” for AUD--we will increase
our understanding of acamprosate mechanism(s) of action and of the underlying pathophysiology of this
disorder, thus helping make it possible to develop better and more effective drugs in the future. In Project 2,
we will take advantage of our extensive experience and success in the application of metabolomics—
particularly when joined with genomics and functional genomics, of our earlier acamprosate clinical trial
performed with P20 funding and of the placebo-controlled acamprosate trial proposed with support from this
application to apply “pharmacometabolomics” and “pharmacometabolomics-informed pharmacogenomics” to
identify molecular and genomic signatures for acamprosate exposure and response in patients suffering from
AUD. We should also emphasize that we propose to rapidly move “beyond biomarkers” to functionally
validate and mechanistically pursue the genes and pathways identified by using cell line-based model
systems and neurons differentiated from iPS cells as well as animal models—studies that will be conducted
in close collaboration with Projects 1 and 4. As described in Project 1, we will utilize sustained abstinence as
our primary phenotype, but we will also take a similar approach to study additional phenotypes identified.
RELEVANCE (See instructions):
This innovative and comprehensive “multiple omics” approach, based on the use of acamprosate as both a
therapeutic agent and a molecular probe, will make it possible to identify molecular and genomic signatures
for drug exposure and drug response while also advancing our understanding of drug action and of disease
pathophysiology.

## Key facts

- **NIH application ID:** 9941010
- **Project number:** 5R01AA027486-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Richard M. Weinshilboum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $604,737
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941010

## Citation

> US National Institutes of Health, RePORTER application 9941010, Alcohol Use Disorder:  Acamprosate Pharmacometabolomics-informed Pharmacogenomics (5R01AA027486-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9941010. Licensed CC0.

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