Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder

Ming Fen Ho, Cheng Zhang, Irene Moon, Brandon J. Coombes, Joanna Biernacka, Michelle Skime, Doo Sup Choi, Paul E Croarkin, Mark A. Frye, Quyen Ngo, Cedric Skillon, Tyler S. Oesterle, Victor M. Karpyak, Hu Li, Richard M. Weinshilboum

Research output: Contribution to journalArticlepeer-review

Abstract

Acamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The identification of predictive biomarkers of acamprosate treatment response in patients with AUD would be a substantial advance in addiction medicine. We designed this study to use proteomics data as a quantitative biological trait as a step toward identifying inflammatory modulators that might be associated with acamprosate treatment outcomes. The NIAAA-funded Mayo Clinic Center for the Individualized Treatment of Alcoholism study had previously recruited 442 AUD patients who received 3 months of acamprosate treatment. However, only 267 subjects returned for the 3-month follow-up visit and, as a result, had treatment outcome information available. Baseline alcohol craving intensity was the most significant predictor of acamprosate treatment outcomes. We performed plasma proteomics using the Olink target 96 inflammation panel and identified that baseline plasma TNF superfamily member 10 (TNFSF10) concentration was associated with alcohol craving intensity and variation in acamprosate treatment outcomes among AUD patients. We also performed RNA sequencing using baseline peripheral blood mononuclear cells from AUD patients with known acamprosate treatment outcomes which revealed that inflammation-related pathways were highly associated with relapse to alcohol use during the 3 months of acamprosate treatment. These observations represent an important step toward advancing our understanding of the pathophysiology of AUD and molecular mechanisms associated with acamprosate treatment response. In conclusion, applying omics-based approaches may be a practical approach for identifying biologic markers that could potentially predict alcohol craving intensity and acamprosate treatment response.

Original languageEnglish (US)
Article number986238
JournalFrontiers in Pharmacology
Volume13
DOIs
StatePublished - Sep 1 2022

Keywords

  • acamprosate
  • alcohol craving
  • alcohol use disorder
  • proteomics
  • TNFSF10
  • treatment outcomes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder'. Together they form a unique fingerprint.

Cite this