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From gene networks to drugs: systems pharmacology approaches for AUD

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Abstract

The alcohol research field has amassed an impressive number of gene expression datasets spanning key brain areas for addiction, species (humans as well as multiple animal models), and stages in the addiction cycle (binge/intoxication, withdrawal/negative effect, and preoccupation/anticipation). These data have improved our understanding of the molecular adaptations that eventually lead to dysregulation of brain function and the chronic, relapsing disorder of addiction. Identification of new medications to treat alcohol use disorder (AUD) will likely benefit from the integration of genetic, genomic, and behavioral information included in these important datasets. Systems pharmacology considers drug effects as the outcome of the complex network of interactions a drug has rather than a single drug-molecule interaction. Computational strategies based on this principle that integrate gene expression signatures of pharmaceuticals and disease states have shown promise for identifying treatments that ameliorate disease symptoms (called in silico gene mapping or connectivity mapping). In this review, we suggest that gene expression profiling for in silico mapping is critical to improve drug repurposing and discovery for AUD and other psychiatric illnesses. We highlight studies that successfully apply gene mapping computational approaches to identify or repurpose pharmaceutical treatments for psychiatric illnesses. Furthermore, we address important challenges that must be overcome to maximize the potential of these strategies to translate to the clinic and improve healthcare outcomes.

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Funding

This review is supported by funding from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH): AA024332 to LF and AA020926 to RDM and to the Integrative Neuroscience Initiative on Alcoholism (INIA)-Neuroimmue Consortium AA012404 to RAH.

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  1. Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, 1 University Station A4800, Austin, TX, 78712, USA

    Laura B. Ferguson, R. Adron Harris & Roy Dayne Mayfield

  2. Intitute for Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA

    Laura B. Ferguson

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Ferguson, L.B., Harris, R.A. & Mayfield, R.D. From gene networks to drugs: systems pharmacology approaches for AUD. Psychopharmacology 235, 1635–1662 (2018). https://doi.org/10.1007/s00213-018-4855-2

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