Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Long COVID.

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

The study expands on a previously-awarded proposal to thoroughly explore the underlying pathophysiology of post exertional malaise (PEM), the hallmark symptom of ME/CFS.

  • David Systrom, MD, PhD
  • Wenzhong Xiao, PhD
  • IRB approval granted for back-to-back non-invasive CPETs and muscle biopsies.
  • 75+ patients have already expressed interest in participating.
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). The study expands on a previously-awarded proposal to thoroughly explore the underlying pathophysiology of PEM.

The researchers will use a 2-Day CPET protocol that has been established previously to examine whether there were any functional changes in the mitochondria. To do this, they will take a biopsy of the vastus lateralis, which is one of the four major muscles in the anterior thigh, and isolate specialized immune cells from blood samples taken before and after exercise.

Dysfunction of the mitochondria has demonstrated decreased ability to use oxygen during exercise and possible interference in energy production. The impact of PEM on ventilatory and pulmonary gas exchange measures will also be assessed.

Specifically, we 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 exercise.

OBJECTIVES

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

1. Assess the relevance of mitochondrial dysfunction after acute exercise to post exertional malaise.

  • Assess mitochondrial electron transport chain function and citrate synthase activity in limb skeletal muscle after exhaustive exercise on two consecutive days.
  • Assess mitochondrial electron transport chain function and citrate synthase activity in peripheral blood mononuclear cells (PBMCs) before and after exhaustive exercise.

2. Determine the prevalence of red blood cell deformability in ME/CFS.

  • Assess changes in peak exercise ventilation and pulmonary gas exchange measures using serial non-invasive cardiopulmonary exercise tests (CPET).
  • Characterize extracellular vesicles (EVs) isolated from ME/CFS patients and controls before and after two-day CPETs.
  • Assess the cytokine, transcriptomic, metabolomic and proteomic profiles in the blood and skeletal muscle in response to exercise.