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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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Skeletal Muscle Dysfunction Research

Study AIM

This Harvard study explored the biological changes that occur in the muscles during Post-exertional Malaise (PEM). The Computation Center is now seeking to identify drug targets to prevent PEM.

LEAD INVESTIGATORS
  • Wenzhong Xiao, PhD
  • Philip Atherton, PhD
  • Paul Greenhaff, PhD
  • David Systrom, MD
Updates and Potential
  • 95 skeletal muscle samples have been studied using Illumina RNA-seq systems by NovoGene
  • There were two studies of healthy aging subjects:
    • 2 weeks bedrest [younger (18-30 years) vs. older (55-65 years)]
      • The older subjects had tremendous genomic response compared to the younger cohort
      • The pathways involved were consistent with immobility
      • Two weeks of physical rehabilitation reversed these genomics
    • 2 months bedrest (young 34 ± 1.8 years)
      • In younger subjects, a comparable genomic response mirrored those changes seen in the two-week study in the older cohort
      • These genomic changes were consistent with those seen after two weeks of bedrest in the older cohort.
The skeletal muscle genomics have been completed and the analysis is underway to include metabolic modelling. Click here to find out more.
STUDY HYPOTHESIS AND DESCRIPTION

Powerful genomic research tools used to understand cancer and heart disease might also help us understand why people with ME/CFS develop post-exertional malaise (PEM). The way that genes in ME/CFS patients behave differently from those in healthy comparable subjects might give tremendous insight for a biomarker or drug targets to combat PEM and fatigue.

The hypothesis is that the inflammation-related recovery mechanisms become dysfunctional in the ME/CFS disease, and this dysregulation causes delayed muscle recovery after exertional stress.

This hypothesis will be tested by analysing nearly 100 muscle biopsy samples from healthy subjects whose ages, sex, and lifestyles match those of ME/CFS patients as closely as possible. Careful comparison to these samples will be critical to detect subtle differences in the genes responsible for a healthy recovery from muscular exercise.

OBJECTIVES

Illustration of muscles of the body from multiple angles.

  • Muscle biopsy samples will be taken from ME/CFS patients both at rest and eventually during their recovery from mild to moderate muscular stress.
  • Comparisons will be made to healthy volunteers also at rest, during recovery from muscular stress, and during immobilization.
  • Using muscle samples, this study will examine the following:
    • Genomics
    • Proteomics
    • Metabolomics
    • Phospho-proteomics
    • Ultrastructural analysis
    • Mitobiogenetic markers.

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.