Leveraging systems pharmacology to advance precision medicine for Gabapentin treatment of AUD

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Project Summary / Abstract The overall goal of this proposal is to leverage systems pharmacology to advance precision medicine for gabapentin treatment of AUD. The current proposal will utilize DNA and RNA samples available from a completed NIAAA sponsored study on Gabapentin Enacarbil Extended – Release (GE-XR) for AUD and resources from our NYU Center for PrecisionMedicine in Alcohol Use Disorder and PTSD. Our Center was created in September 2018 with funding from an NIAAA P01 “Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD”. Our NYU Center focuses on advancing precision medicine for alcohol use disorders, including those comorbid with PTSD, utilizing molecular and circuit markers and advanced computational models for determining responders and non-responders to treatment. The primary aims focused to advance precision medicine by discovering pharmagenomic, pharmacoepigenomic and pharmacotranscriptomic predictors of individual differences in responses to GE-XR treatment of AUD. There will be eight pathways to be prioritized as part of the primary aims of the proposal. The pathways are: voltage sensitive channels, excitatory and inhibitory amino acids, gabapentin amino acid transporters, serotonin pathway, rewarding properties of alcohol, neuor- inflammatory, apoptotic/oxidative stress and neurotrophic factors. The secondary aim focuses on discovering novel targets and pathways. The group will utilize polymorphisms, epigenetic marks, transcripts and miRNA markers for discovery of novel targets and pathways for predicting individual responses in alcohol use in participants. The data to be ascertained from the proposed aims have potential for discovery of novel genomic features to predict responders and non-responders for GE-XR treatment of AUC. These discoveries would significantly contribute to the NIAAA goal of advancing precision medicine within the domain of AUC. More broadly, the novel computational methods that we will advance in this proposal for modelling genomic predictors of likely responders hold promise for advancing precision medicine for other medications for AUD and for personalized treatments of other substance use disorders.