Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking Back on Treatments

Eloy Almenar-Pérez,Lubov Nathanson,Teresa Sánchez-Fito,Tamara Ovejero,Elisa Oltra

doi:10.3390/pharmaceutics11030126

Abstract

Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are diseases of unknown etiology presenting complex and often overlapping symptomatology. Despite promising advances on the study of miRNomes of these diseases, no validated molecular diagnostic biomarker yet exists. Since FM and ME/CFS patient treatments commonly include polypharmacy, it is of concern that biomarker miRNAs are masked by drug interactions. Aiming at discriminating between drug-effects and true disease-associated differential miRNA expression, we evaluated the potential impact of commonly prescribed drugs on disease miRNomes, as reported by the literature. By using the web search tools SM2miR, Pharmaco-miR, and repoDB, we found a list of commonly prescribed drugs that impact FM and ME/CFS miRNomes and therefore could be interfering in the process of biomarker discovery. On another end, disease-associated miRNomes may incline a patient’s response to treatment and toxicity. Here, we explored treatments for diseases in general that could be affected by FM and ME/CFS miRNomes, finding a long list of them, including treatments for lymphoma, a type of cancer affecting ME/CFS patients at a higher rate than healthy population. We conclude that FM and ME/CFS miRNomes could help refine pharmacogenomic/pharmacoepigenomic analysis to elevate future personalized medicine and precision medicine programs in the clinic.

Highlights

Fibromyalgia (FM) is a debilitating disorder characterized by a low pain threshold and muscle tenderness accompanied by bowel abnormalities, sleep disturbances, depressive episodes, cognitive problems, and chronic pain [1,2,3,4]
Though commonly comorbid with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease showing a complex clinical pathophysiology [5,6,7,8,9,10,11], these syndromes have been classified by the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), with separate codes (M79.7 and R53.82 or G93.3 if post-viral, for FM and ME/CFS, respectively) [12]
We have evaluated miRNA–target gene–drug interactions of differentially expressed (DE) miRNAs in FM and ME/CFS as an approach to determine the ability or predisposition of these patients to respond to common clinical treatments for diseases in general, including diseases other than FM and ME/CFS, which may appear comorbid at some point in FM and ME/CFS patients’ lives

Summary

Introduction

Fibromyalgia (FM) is a debilitating disorder characterized by a low pain threshold and muscle tenderness accompanied by bowel abnormalities, sleep disturbances, depressive episodes, cognitive problems, and chronic pain [1,2,3,4]. Post-exertional malaise (PEM), a clinical hallmark of ME/CFS, together with additional clinical and biological parameters differing between these two diseases [19,20,21,22,23,24] seem to support a distinct underlying pathophysiology and possibly etiology for FM and ME/CFS. Aimed at clarifying this diagnostic conflict through an improved understanding of the biology of disease onset and evolution, some research groups, ours included, have set out to identify molecular biomarkers of these illnesses [25]

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Discussion

Conclusion