1. Sign our petition calling on Cochrane to withdraw their review of Exercise Therapy for CFS here.
    Dismiss Notice
  2. Guest, the 'News in Brief' for the week beginning 18th March 2024 is here.
    Dismiss Notice
  3. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice

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

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

  1. MeSci

    MeSci Senior Member (Voting Rights)

    Messages:
    4,437
    Location:
    Cornwall, UK
    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.
     
    andypants, Milo, merylg and 10 others like this.
  2. Andy

    Andy Committee Member

    Messages:
    21,803
    Location:
    Hampshire, UK
    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)

    Messages:
    3,309
    Why are they using Fukuda?
     
    Mithriel, RedFox, andypants and 2 others like this.
  4. Andy

    Andy Committee Member

    Messages:
    21,803
    Location:
    Hampshire, UK

Share This Page