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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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Metabolic Trap Study

STUDY AIM
Beginning in 2018, the aim of this study was to test the hypothesis developed by Dr Phair that a crucial component of metabolism in ME/CFS patients appears to be “trapped” in an unhealthy state.
LEAD INVESTIGATORS

  • Robert D. Phair, PhD
  • Julie Wilhelmy, PhD
  • Ronald W. Davis, PhD

UPDATES AND POTENTIAL
The modeling progress of this study takes into account the compartmentalization of the Trp (Tryptophan) to Kyn (Kynurenine) pathways. Further, these pathways are being validated in yeast models. In parallel, there are human cell assays that are under development to evaluate these pathways in human cells, monocytes/macrophages and the analytical methods are underway.

STUDY HYPOTHESIS AND DESCRIPTION

The metabolic trap theory emerged from the genetic and metabolomics data from the Severely ill Patients Study (SIPS). Using previously published work, Dr Phair has developed a computational program that can model the flow of metabolism throughout the body and its cells.  Using this technology, Dr Phair can determine any points that may disrupt the flow using genomic and metabolic information and this has led to the hypothesis of a metabolic trap that occurs in ME/CFS patients at the point in metabolism where tryptophan is converted to serotonin and kynurenine.

 OBJECTIVES

Illustration of Biomolecules - Metabolism

To test the hypothesis, experiments were initiated to measure the levels of tryptophan and kynurenine in cells from ME/CFS patients. This is a complicated procedure, as taking cells out of the body without disrupting their inherent metabolism is fraught with problems.

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.