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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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Cellular Nitrogen and Energy Metabolism in ME/CFS

STUDY AIM
This project aims to test the nitrogen hypothesis, which is that damaging, nitrogen-containing by-products of energy metabolism accumulate more readily in the cells of ME/CFS patients.
LEAD INVESTIGATORS
  • Daniel Missailidis, PhD
  • Robert Phair, PhD
  • Paul Gooley, PhD
  • Sarah Annesley, PhD
  • Christopher Armstrong, PhD
UPDATES AND POTENTIAL
  • Lymphoblast experiments are completed.
  • We have expanded to look at cells with known genetic anomalies.
  • Both the lymphoblast samples and cells with mutations have been prepared and are currently producing metabolite data for analysis.
  • Expecting both projects to be completed in 2025.
  • There will be 3 publications for this work.

STUDY HYPOTHESIS AND DESCRIPTION

ME/CFS, a condition diagnosed by symptoms like extreme tiredness after exertion (known as post-exertional malaise), ongoing fatigue, and mental cloudiness or “brain fog,” may stem from a basic problem with how energy is made and used in the body.

We hypothesize that in ME/CFS, nitrogen compounds might be mishandled in immune cells because the mitochondria (energy factories of the cell) are using amino acids (building blocks of proteins) to make energy. To explore this idea, scientists will grow immune cells from blood samples and feed them special types of sugar, fats, and amino acids that can be tracked. This will allow them to see how the metabolism of these cells in ME/CFS patients is different from people without the condition.

This study uses innovative methods to deepen our understanding of ME/CFS and possibly uncover the root causes of its symptoms.

 OBJECTIVES

A gloved hand holds sample tube with a label. In the background are several more tubes in a rack.

  1. Observe how amino acids are used by cells from ME/CFS patients compared to healthy controls.
  2. Observe how sugars are used by cells from ME/CFS patients compared to healthy controls.
  3. Observe how fats are used by cells from ME/CFS patients compared to healthy controls.
  4. Observe the usage rate of sugars, fats, and amino acids in ME/CFS and controls.
  5. Test the Nitrogen Hypothesis.

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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.