Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules |
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| Institution: | 1. Simmaron Research Institute, 948 Incline Way, Incline Village, NV 89451, United States of America;2. Simmaron R&D lab, Technology Innovation Center, 10437 W Innovation Drive, Wauwatosa, WI 53226, United States of America;3. Coppe Laboratories, W229N1870 Westwood Dr, Waukesha, WI 53186., United States of America;1. Genetic Research About Stress and Psychiatry (GRASP), Department of Neurosciences, KU Leuven, Leuven, Belgium;2. Center for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium;3. Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium;4. IDEWE, External Service for Prevention and Protection at Work, Heverlee, Belgium;5. Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium;6. Research Department of Clinical, Educational and Health Psychology, University College London, London, UK;7. Blood Service, Belgian Red Cross-Flanders, Mechelen, Belgium;8. University Psychiatric Center, Leuven, Belgium;9. Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium;10. VIB Center for Cancer Biology, VIB, Leuven, Belgium;11. Department of Epidemiology and Prevention, IRCCS Neurologico Mediterraneo Neuromed, Pozzilli, Italy |
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| Abstract: | PurposeMyalgic 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.MethodsHere 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.FindingsThe 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.ImplicationsThe findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation–based treatment strategies. |
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| Keywords: | bioinformatics chronic fatigue syndrome drug repositioning myalgic encephalomyelitis pharmacogenomics |
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