Treatment avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a split-gender pharmacogenomic study of gene-expression modules, by Mary G Jeffrey, Lubov Nathanson, Kristina Aenlle, Zachary M Barnes, Mirza Baig, Gordon Broderick, Nancy G Klimas, Mary Ann Fletcher, Travis JA Craddock in Clinical Therapeutics vol 41, issue 5, May 2019, pages 815-835.e6 [https://doi.org/10.1016/j.clinthera.2019.01.011]
Research 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.
