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Treatment avenues in ME/CFS: A split-gender pharmacogenomic study of gene-expression modules, 2019, Jeffrey, Broderick. Klimas et al

Discussion in 'BioMedical ME/CFS Research' started by MeSci, Mar 9, 2019.

  1. MeSci

    MeSci Senior Member (Voting Rights)

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    Source: Clinical Therapeutics

    Preprint

    Date: March 6, 2019

    URL:
    https://www.sciencedirect.com/science/article/abs/pii/S0149291819300475

    Treatment avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A split-gender pharmacogenomic study of gene-expression modules
    ----------------------------------------------------------
    Mary G. Jeffrey(1,2), Lubov Nathanson(1,3), Kristina Aenlle(1,3,4), Zachary M. Barnes(1,4,5,6), Mirza Baig(1), Gordon Broderick (1,2,3,7,8), Nancy G. Klimas(1,2,3), Mary Ann Fletcher(1,3,4), Travis J.A. Craddock(1,2,3,9,*)

    1 Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA

    2 College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA

    3 Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA

    4 Miami Veterans Affairs Medical Center, Miami, FL, USA

    5 Miller School of Medicine, University of Miami, Miami, FL, USA

    6 Diabetes Research Institute, University of Miami, Miami, FL, USA

    7 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    8 Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, USA

    9 Department of Computer Science, Nova Southeastern University, Ft. Lauderdale, FL, USA

    * Corresponding author. Institute for Neuro-Immune Medicine, Nova Southeastern University, 3301 College Avenue, Fort Lauderdale, FL 33314, USA. Email: tcraddock@nova.edu

    Received 7 November 2018

    Revised 9 January 2019

    Accepted 18 January 2019

    Available online 6 March 2019.

    Abstract

    Purpose

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisymptom illness impacting up to 1 million people in the United States. As the pathogenesis and etiology of this complex condition are unclear, prospective treatments are limited. Identifying US Food and Drug Administration-approved drugs that may be repositioned as treatments for ME/CFS may offer a rapid and cost-effective solution.

    Methods

    Here we used gene-expression data from 33 patients with Fukuda-defined ME/CFS (23 females, 10 males) and 21 healthy demographically comparable controls (15 females, 6 males) to identify differential expression of predefined gene-module sets based on nonparametric statistics.

    Differentially expressed gene modules were then annotated via over-representation analysis using the Consensus Pathway database.

    Differentially expressed modules were then regressed onto measures of fatigue and cross-referenced with drug atlas and pharmacogenomics databases to identify putative treatment agents.

    Findings

    The top 1% of modules identified in males indicated small effect sizes in modules associated with immune regulation and mitochondrial dysfunction. In females, modules identified included those related to immune factors and cardiac/blood factors, returning effect sizes ranging from very small to intermediate (0.147<Cohen delta<0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor alpha, transforming growth factor beta, and metabolic and cardiac modules were strongly correlated with multiple composite measures of fatigue. Cross-referencing identified genes with pharmacogenomics data indicated immunosuppressants as potential treatments of ME/CFS symptoms.

    Implications

    The findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation-based treatment strategies. (Clin Ther. 2019;41:XXX-XXX) (c)

    2019 Elsevier Inc.
     
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  2. Andy

    Andy Committee Member & Outreach

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    33 patients, Fukuda criteria, 23 female, 10 male
    Sci Hub link, https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S0149291819300475
     
  3. Alvin

    Alvin Senior Member (Voting Rights)

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    Why are they using Fukuda?
     
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