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Stress-Activated MicroRNAs
in ME / CFS Pathogenesis

Study Aim

 

The purpose of this project is to develop a clinical intervention enabling the study of people with ME/CFS, and to evaluate changes in miRNAs in response to this clinical intervention.

LEAD INVESTIGATOR
  • Alain Moreau, PhD
Results / Reason for Discontinuation
  • This strategy led us to identify 32 circulating microRNAs in a case-control cohort.
  • Several of the miRNAs identified in our discovery cohort are associated with inflammation, regulation of immunity, and/or a physiological response to exercise (endurance regulators).
  • Implementation of bioinformatics tools like a Machine Learning algorithm (Random Forest Algorithm) led to a validation of a first diagnostic panel of 8 microRNAs (miR-28-5p, miR-29a-5p, miR-127-3p, miR-140-5p, miR-374b-5p, miR-486-5p, miR-3620-3p and miR-6819-3p) using a dataset of individuals with ME/CFS and matched healthy controls.
  • This panel has a predictive accuracy of 90% with a sensitivity of 100% and a specificity of 75% when the expression of each microRNA is compared after the stress test versus their respective values at baseline (without stimulation). Conversely, when only the baseline values are used (without the stress test), the predictive accuracy is lowered to 60% with a sensitivity of 71% and a specificity of 33% (non-specific). These preliminary results clearly indicated the superiority of our stress test approach to reveal the molecular signature underlying ME/CFS.
  • This approach led also to an unbiased method to separate the persons with ME/CFS, called clustering, along three distinct clusters showing specific correlations between each cluster and symptom severity. Indeed, persons with ME/CFS classified in cluster 1 exhibit less general fatigue than those classified into cluster 2 and 3, while individuals in cluster 3 suffer more severe sleep disturbances and PEM.
  • Interestingly, high expression of specific circulating microRNAs could help in predicting the response to specific treatments like Ampligen, Rituximab, and many others.
  • To find out more about the outcomes of this study, read the publication:
  • The next phase of our investigation into microRNAs continued with the MAESTRO project.

Study Hypothesis and Description

Studying microRNAs might help to bridge the conceptual gap between genetic predisposition and environmental factors causing ME/CFS or exacerbating specific symptoms. Equally important, the design of a portable clinical intervention will allow for the investigation of severely ill persons with ME/CFS, especially the ones that are housebound.

We designed a clinical intervention, safely producing post-exertional malaise (PEM), a hallmark symptom of ME/CFS. We hypothesized that a standardized stress test inducing PEM will reveal a more specific disease signature associated with ME/CFS symptoms. In that context, we investigated the role of circulating microRNAs, which are small non-coding RNA molecules that can be detected in the blood as well as in other biological fluids.

 

Objectives

  • Evaluate the miRNA profile of patients before and after a stress test.
  • Correlate the resulting miRNA profile to specific symptoms.

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Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation®

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