Hi everybody,
Hi Dr. Phair (
@HTester)
This is my first post on this forum though I am a member of the forum since 2011.
Sorry for my English, I'm not a native speaker.
I really liked your metabolic trap hypothesis, I've watched the conference talks and read the newly published paper. I'm not a scientist but as other persons with ME/CFS I'm really interested in ME/CFS science and its outcomes.
When I googled articles to find out more about kynurenine pathway, all I get is articles that link the kynurenine pathway and its metabolites to neurodegenerative diseases and to my surprise more commonly its overactive state. Also IDO2 is linked more with its proinflammatory role in some autoimmune diseases in several papers.
The kynurenine pathway and neurodegenerative disease.
https://www.ncbi.nlm.nih.gov/pubmed/25773161
IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119657/
IDO2 in immunomodulation and autoimmune disease
https://www.frontiersin.org/articles/10.3389/fimmu.2014.00585/full
On the other side there are papers stating that inhibition of kynurenine pathway or modulating it could be therapeutic in some neurogical diseases:
Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/j.1742-4658.2012.08487.x
Inhibiting the kynurenine pathway in spinal cord injury: multiple therapeutic potentials?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199950/
Inhibitors of the kynurenine pathway
https://www.frontiersin.org/articles/10.3389/fmolb.2019.00003/full
So my question is: Is it possible that if the theory of metabolic trap is correct, that the trap is not only pathological state but also protective state that acts as emergency brake to not cause bigger damage? But if that is correct, then it is not a good idea to try to open the kynurenine pathway if the chronic trigger is still present.
And my second question and the thing I was missing in the paper: How precisely nonfunctional kynurenine pathway explains ME/CFS symptoms or what is the main possible reason that this pathway is cause of ME/CFS symptoms specifically?
Thank you for your time.