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

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Kynurenine Trial in ME/CFS

STUDY AIM
The purpose of this study is to understand potential disturbances in the tryptophan metabolism and to test the benefits of treating people with ME/CFS with Kynurenine.
LEAD INVESTIGATORS
  • Jonas Bergquist, MD, PhD, Prof, Director ScD
  • Kumari Ubhayasekhera, PhD
  • Sandy Abujrais. PhD Student
UPDATES AND POTENTIAL

This study is on hold, pending further discussions.

IRB approval has been obtained and trial conducted in healthy volunteers.

Analysis of preliminary data for ME/CFS patients did not indicate significant disturbances in the Kynurenine pathway so further trials steps on hold.

Discussion should be pursued around whether to shift this limited funding to other more promising candidates for trials.

Data from animal models reveal the impact of introducing Kynurenine related metabolites but not yet showing significant impacts at the intracellular level. Perhaps other paths of inquiry could be pursued.

Kynurenine pathway is still important but not clear how it is involved in post- viral induced neurocognitive disturbances.

STUDY HYPOTHESIS AND DESCRIPTION

“Those of us working on the IDO metabolic trap hypothesis for ME / CFS are really interested in the study proposed by Dr. Bergquist and his team in Uppsala, and recently funded by OMF. Here’s why:

Suppose that some brain cells in a particular brain nucleus are in the IDO metabolic trap. This means that in those cells the concentration of tryptophan is too high, and the concentration of kynurenine is too low. Supplying an outside source of kynurenine, as Dr. Bergquist proposes, could conceivably solve part of the problem by allowing those brain cells to make the neuroactive metabolites of kynurenine that they cannot make if the metabolic trap has been sprung.

So, the clinical trial might improve symptoms caused by too little kynurenine or too little kynurenic acid, a known neuro-protectant. Dr. Bergquist’s expertly designed clinical trial of kynurenine in ME / CFS to improve brain fog, memory, and headache is both important and timely.”

– Robert Phair, Ph.D. The Metabolic Trap

OBJECTIVES

Participants will be randomized to either receive Kynurenine or a placebo for a period of three months and then after a “washout” period, patients will switch to an additional three-months of Kynurenine or placebo in a crossover design.

This design does not require healthy controls and instead focuses on whether Kynurenine supplementation has any benefit above placebo in people with ME / CFS.

The main study endpoints will be the effects of supplemental Kynurenine to improve cognitive impairment (“brain fog”), memory and headache. Patients will also be asked to register their activity by using wearable sensors and have biological samples taken for further testing.

New methods have been developed under Dr. Bergquist to measure the metabolic pathways relevant to Kynurenine. These new methods are used to identify people with ME / CFS that have low Kynurenine in the plasma. This method will also be used to monitor the metabolic effects of Kynurenine supplementation during the trial.

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.