# Alcohol Use Disorder: Acamprosate Pharmacometabolomics-informed Pharmacogenomics

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $415,165

## Abstract

PROJECT SUMMARY/ABSTRACT
Acamprosate and naltrexone are major medications used in the treatment of alcohol use disorder (AUD).
However, response to treatment with these drugs is variable, with only ~50% of patients achieving optimal
outcomes. As a result, it would be important to identify molecular mechanisms underlying individual variation in
AUD drug treatment outcomes. That information could potentially facilitate the development of individualized
AUD pharmacotherapy regimens as well as the development of novel AUD therapeutic agents. During the
current funding cycle, we performed a series of “Pharmaco-Omic” studies designed to identify biomarkers
associated with acamprosate response for AUD patients enrolled in our Mayo Clinic Center for Individualized
Treatment of Alcohol Dependence (CITA) clinical trial—one of the largest acamprosate AUD clinical trials
and one for which we have generated a series of multiple omics datasets. Using those data, we identified
novel biomarkers associated with variation in acamprosate treatment outcomes. Those biomarkers included, for
example, the FNDC4 gene and a series of other genes—genes which we now propose to study further by
performing functional studies of the AUD biomarkers that we have already identified and to extend those studies
to include a series of protein biomarkers for both AUD drug response and AUD pathophysiology. Finally, we
will also expand our studies to include the application of iPSC-derived brain organoids from both our
AUD patients and control subjects to make it possible to identify genes and biological pathways that
contribute to acamprosate and naltrexone treatment response. In summary, the studies proposed in this
application represent a systematic attempt to identify and study molecular mechanisms underlying and
associated with variation in AUD drug treatment response phenotypes and AUD clinical outcomes in
response to drug therapy. Our use of “multiple omics” to study samples from AUD patients treated with these
drugs, followed by “functional omic” studies of those samples and concluding with the generation and study of
patient-derived brain organoids generated from the same patients make this series of studies truly unique
and—based on our preliminary data—highly promising for the identification of novel candidate genes and
pathways. The results of the proposed studies would represent a significant step toward greater understanding
of the biology of acamprosate and naltrexone treatment response in AUD, potentially leading to the development
of better and more effective AUD drug therapy, an outcome that would represent a significant advance in the
treatment of this disorder.

## Key facts

- **NIH application ID:** 10978333
- **Project number:** 2R01AA027486-06A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Ming-Fen Ho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $415,165
- **Award type:** 2
- **Project period:** 2024-09-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978333

## Citation

> US National Institutes of Health, RePORTER application 10978333, Alcohol Use Disorder: Acamprosate Pharmacometabolomics-informed Pharmacogenomics (2R01AA027486-06A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10978333. Licensed CC0.

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