IDO Metabolic Trap Hypothesis Published Today

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To follow up a bit, Dr. Davis did mention in his speech at the Albert Einstein College of Medicine that the IDO1 inhibiting cancer drugs caused extreme fatigue. There were a few drugs that were developed to inhibit IDO1. The one I am assuming he’s talking about is Indoximod, due to it having the highest percentage of subjects with fatigue as a side effect (58.6%,“Biology of T Cells - Part A“). @HTester or anyone for that matter, feel free to correct me if I’m missing the mark on this.
 
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I just read this forum category. I wrote a research paper on IDO a number of years ago. Yes - antigen presenting cells create a tryptophan sink to pull extracellular trytophan to limit its availibility infection. This is one of the primary reasons that cd4 helper counts are so low in HIV (and a subset of CFS patients).

As to the NO link, Henrich kremer’s work is groundbreaking and under appreciated in this regard. Absolute must read.
 

FMMM1

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I just read this forum category. I wrote a research paper on IDO a number of years ago. Yes - antigen presenting cells create a tryptophan sink to pull extracellular trytophan to limit its availibility infection. This is one of the primary reasons that cd4 helper counts are so low in HIV (and a subset of CFS patients).

As to the NO link, Henrich kremer’s work is groundbreaking and under appreciated in this regard. Absolute must read.
Thanks for this.

There's a literature review here which is interesting:
https://www.spandidos-publications.com/10.3892/mmr.2018.8537

Coupled with Bupesh Prusty's work on mitochondrial fragmentation i.e. as an immune response; this (accumulation of intracellular tryptophan) seems to support immune dis-regulation as a potential cause of ME.

How would you test the hypothesis e.g. test tryptophan levels in antigen presenting cells?
 
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Thanks for this.

There's a literature review here which is interesting:
https://www.spandidos-publications.com/10.3892/mmr.2018.8537

Coupled with Bupesh Prusty's work on mitochondrial fragmentation i.e. as an immune response; this (accumulation of intracellular tryptophan) seems to support immune dis-regulation as a potential cause of ME.

How would you test the hypothesis e.g. test tryptophan levels in antigen presenting cells?
I dont think the problem is intracellar tryptophan in the immune cells, rather, its the lack of extracellular tryptophan caused by it. Lack of tryptophan results in less serotonin and melatonin as well as significant immune dysfunctionin terms of natural killer cell function and other immune functioning.
 
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I dont think the problem is intracellar tryptophan in the immune cells, rather, its the lack of extracellular tryptophan caused by it. Lack of tryptophan results in less serotonin and melatonin as well as significant immune dysfunctionin terms of natural killer cell function and other immune functioning.
Also, IDO is upregulated in response to various cytokines such as interferon gamma, tnfa, il-6, etc. It gets complicated because interferon beta is often upregulated in chronic viral infections and restoration of interferon gamma with a reduction in interferon beta can sometimes clear them (hpv for example). Mixed viral and bacterial infections are very problematic in this regard.
 
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I just read this forum category. I wrote a research paper on IDO a number of years ago.
@HTester who is researching the IDO Metabolic trap started a thread here. It's long, but you may want to just read his posts. He doesn't post much.
https://forums.phoenixrising.me/threads/the-ido-metabolic-trap-guy.62727/

There is a write-up two years ago with his contact details
https://www.healthrising.org/blog/2018/04/03/a-metabolic-trap-for-chronic-fatigue-syndrome-me-cfs/
 
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The issue with IDO is that it can be chronically activated to suppress both pathogens as well as inhibit tissue damage in immunologically privelaged sites like the heart and brain. Think of it as a sort of a truce between host and pathogen. For example, elevated kynurenin is often found in the cfs fluid of neuroborreliosis. IDO breakdown metabolites like quinolinic acid are also neurotoxic.

In lieu of really good direct antiviral/antibiotics, lifting the IDO breaks can lead to some pathology so its a catch 22. Other than 1-methyl-tryptophan which is a potent IDO inhibitor, compounds in neem appear to inhibit IDO as well.

I think broad spectrum natural compounds in sufficient doses over time may be the way to go to work down pathogen loads before lifting the immune/IDO break. Like many of you, I read tons of posts from all kinds of forums and have come to the conclusion that single pathogen chasing is unlikely to yield results in many cases. There is so much overlap between chronic lyme, cfs, cebv, candida, mycoplasma etc. Most people dont know with certainty what the main culprit is. Probably several. The best antecdotal results I have seen have been with broad sprectrum higher dose natural antimicrobials dosed over longer periods if time.
 

bctjr1993

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Yes, you can hear Ron mention what is very likely a reference to CRISPR-based gene cutting and pasting at 56:30 here: ("as we learn how to do genetic manipulation, and that's coming right around the corner")
Actually, going back and watching the video that I was talking about, when discussing how the might reverse the trap, it wasn't gene editing they mentioned, but rather molecule screening.