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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

  • 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.
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