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Itaconate Trap Study

Study AIM

This project aims to look at metabolic traps in central carbon metabolism that lead to observed altered energy production pathways in ME/CFS.

LEAD INVESTIGATORS

  • Christopher Armstrong, PhD

  • Rob Phair, PhD

Updates and Potential
  • Constructed the differential equation model for the TCA cycle.
  • Developed the itaconate trap hypothesis by looking for mechanisms that prioritise the use of amino acids for energy production.
  • Itaconate cycle can be initiated by pathogens specifically via innate immune signals (IFN-alpha).
  • Currently exploring the relationship between IFN-alpha, itaconate, cellular metabolism, and ME/CFS.
STUDY HYPOTHESIS AND DESCRIPTION

One of the key metabolic theses aiming to explain ME/CFS symptoms is the dysregulated nitrogen metabolism theory proposed by Armstrong and colleagues. Three features of this theory make it attractive:

1) it is consistent with the observed shift from carbohydrate to alternative sources of energy (amino acids and fatty acids),

2) it predicts a reduction in oxygen consumption consistent with a hypometabolic state, and

3) it predicts overproduction of ammonia, a known neurotoxin that could explain ME/CFS neurological symptoms. One underdeveloped aspect of the nitrogen metabolism theory of ME/CFS is the mechanistic chain of events connecting the initial infectious or traumatic trigger to a chronically altered state of central carbon and mitochondrial metabolism.

This computational proposal aims to fill that gap by testing mechanisms that have the potential for switch-like or bistable behavior.

OBJECTIVES

  • Explore the itaconate trap and other potential traps in central carbon metabolism.
  • Build pathways of central carbon metabolism.
  • Develop kinetic models to try predict potential “weakness” points.
  • Test the hypothesis experimentally.
Other links you might be interested in:
What Is ME/CFS?
Information from U.S. Government Agencies
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(EIN# 26-4712664). All donations are tax-deductible to the extent allowed by law.

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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®

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