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

Donate
Sign Up
Main Menu

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

Study AIM

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.

LEAD INVESTIGATORS
  • David Systrom, MD, PhD
  • Wenzhong Xiao, PhD
Updates and Potential
  • Using a previously established 2-Day CPET protocol, the researchers will determine whether functional changes within the mitochondria were present by performing a biopsy of the vastus lateralis, one of four major muscles in the anterior thigh, as well as isolation of specialized immune cells from pre and post exercise blood draws. Dysfunction of the mitochondria have 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, 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.
  • Additional novel approaches of this study include the isolation of extracellular vesicles (EVs) which can be isolated from blood after release from skeletal muscles, as well as exploring the role of red blood cell deformability in potentially inhibited oxygen delivery.
STUDY HYPOTHESIS AND DESCRIPTION

The hallmark symptom of ME/CFS is the flu-like worsening of symptoms after physical, mental, or emotional exertion known as post exertional malaise (PEM). The underlying mechanism behind this response is currently unknown, and this study aims to contribute useful insights to begin filling this gap. Twenty ME/CFS patients (10 recent and 10 historical) and 10 controls will complete 2-Day serial cardiopulmonary exercise tests (CPET) to not only stimulate physical exertion but also gather pulmonary gas exchange data in these groups. In addition, muscle biopsies after each CPET as well as pre and post blood draws will be performed to provide further mechanistic insights into PEM.

OBJECTIVES

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.
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.
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.
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.