Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules.

Author(s)

Mary G Jeffrey
Lubov NathansonFollow
Kristina Aenlle
Zachary M Barnes
Mirza Baig
Gordon Broderick
Nancy G KlimasFollow
Mary Ann FletcherFollow
Travis Craddock, Nova Southeastern UniversityFollow

Document Type

Article

Publication Date

5-1-2019

Publication Title

Clinical Therapeutics

Volume

41

Issue/Number

5

First Page

815

ISSN

1879-114X

Last Page

835

Abstract/Excerpt

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 δ < 0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor α, transforming growth factor β, 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.

DOI

10.1016/j.clinthera.2019.01.011

NSUWorks Citation

Jeffrey, M., Nathanson, L., Aenlle, K., Barnes, Z., Baig, M., Broderick, G., Klimas, N., Fletcher, M., Craddock, T. (2019). Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules.. Clinical Therapeutics, 41(5), 815-835.
Available at: https://nsuworks.nova.edu/cps_facarticles/1689