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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® Canada
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Investigation into Post-Exertional Malaise
Between Historical and Recent ME/CFS

Study AIM

This study explores the biological changes that occur in the muscles during post-exertional malaise (PEM), both in historical cases of ME/CFS and cases of Long COVID that meet the criteria for ME/CFS.

LEAD INVESTIGATORS
  • David Systrom, MD, PhD
  • Wenzhong Xiao, PhD
Updates and Potential
  • This study has enrolled approximately one-third of its total participants.
  • Collaborations have been established with Ron Davis at Stanford, Maureen Hanson at Cornell, Alain Moreau at Montreal, and Rob Wust at Amsterdam to receive and analyze the samples.
STUDY HYPOTHESIS AND DESCRIPTION

The hallmark symptom of ME/CFS is the flu-like worsening of symptoms after physical, mental, or emotional exertion. This is known as post-exertional malaise (PEM).

Dysfunction of the mitochondria has demonstrated decreased ability to use oxygen during exercise and possible interference in energy production. The researchers will investigate mitochondrial dysfunction during PEM in a biopsy of the vastus lateralis, one of the four major muscles in the anterior thigh. The impact of PEM on ventilatory and pulmonary gas exchange measures will also be assessed.

Specifically, the team will look at changes in how the patients utilize oxygen, their achieved workload, and how efficiently they respired at peak exercise and at the ventilatory threshold. (The ventilatory threshold is also known as the point at which the body becomes more dependent on acquiring energy from mechanisms not involving oxygen.)

With this data, the researchers will compare measures within and between groups to demonstrate the effect of PEM in ME/CFS patients due to exertion.

OBJECTIVES

Researcher conducting a VO2 Max test on a patient on an elliptical machine.

  • Muscle biopsy samples will be taken from patients both at rest and during their recovery from mild to moderate muscular stress. Patients fall into one of five groups:
    • ME/CFS with good oxygen extraction at peak exercise
    • ME/CFS with poor oxygen extraction at peak exercise
    • Long COVID with good oxygen extraction at peak exercise
    • Long COVID with poor oxygen extraction at peak exercise
    • Symptomatic controls that do not experience PEM
  • Using muscle samples, analyses in this study will include the following:
    • Metabolomics
    • Proteomics
    • Transcriptomics

Consent management

Consent Preferences

Data Subject Access Request (DSAR) Form 

Microvesicles and viral sequencing
Microvesicles are a type of extracellular vesicle that is released from the cell membrane. Vesicles are small, fluid-filled sacs or vacuoles within the body. Sequencing is a technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA (or viral) molecule.
NMR Metabolomics
NMR (Nuclear Magnetic Resonance) is an instrument/tool used to perform metabolic studies, metabolic profiling, and metabolomics in biofluids and tissues for more than 40 years using magnetic fields. There is a very close connection between metabolic measurements and NMR. This connection has flourished because of NMR’s many unique strengths for characterizing complex mixtures’ chemical composition.
Proteomics
The large-scale study of proteins, which are large, complex molecules that are required for structure, function, and regulation of the human body's tissues and organs.
Autoantibodies
Antibodies that react with self-molecules and that occur in healthy individuals and are referred to as natural antibodies or autoantibodies.
Extracellular DNA for viral reactivation and Mitochondrial DNA
exDNA (extracellular DNA), exDNA is often secreted actively and is used to perform several tasks, thereby offering an attractive target or tool for biotechnological, medical, environmental, and general microbiological applications. Viruses are intracellular parasites that rely to a significant extent on the host cell for replication. Viral reactivation occurs when an active replication of the viral genome results in a lytic (degradation of the cell) infection characterized by the release of new progeny (descendant) virus particles.
Immune cell profiling
The immune system has many important regulatory roles in disease development and progression. Given the emergence of effective immune therapies, reliable predictors of response are needed. Immune cell profiling determines response by evaluating immune cell populations from treated and untreated samples. For our purposes, we will evaluate the white blood cell response to the viral infection using a process called “Cytof.”
Leukocyte Genomics
A leukocyte is a colorless cell circulating in the blood and body fluids and is involved in counteracting foreign substances and disease. A genome is all genetic material of an organism. Genomics is a biology field focusing on the structure, function, evolution, mapping, and editing of genomes. Therefore, leukocyte genomics is the study of all genetic material of leukocytes.
Metabolomics
Metabolomics is a way to study metabolism – that is, through measuring amounts of the metabolites (small molecules) produced by our bodies as we convert food into energy and other molecules that our cells need to survive. Metabolomics technology is ‘large-scale,’ meaning that several thousand metabolites can be measured from a single sample of e.g., blood or urine.
Micro RNA
Cells use Micro RNA to control whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.