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OMF Kynurenine trial

Springbok1988

Senior Member
Messages
155
Daily administration of BB536 was found .. to decrease the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan.
Wouldn’t the goal be to increase the ratio of Kyn to Trp? We want more Kyn and less Trp. Or am I misunderstanding something?
 
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ZeroGravitas

Senior Member
Messages
141
Location
UK
Anyone know the status on the trial?

Is the info in the left side bar of this OMF website page the most up to date..?:
  • 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.
  • Animal model is now under investigation to make it possible to get intracellular monitoring abilities.
So, things didn't look as expect and resources were shifted to other investigations. But animal models may still be in play...?

Is that top point what Dr Phair was referring to back in Dec 2020, here?:
as soon as it becomes possible we will measure the kynurenine pathway flux in ME/CFS patient blood monocytes

I'm looking back at all this to see what happened, in the new context of the Dutch paper finding massively *elevated* IDO2 activity producing *excess* kynurenine in a feedback loop, via AhR (aryl hydrocarbon receptor).

Which, if correct (and applicable to pwME as well as those studied with PASC), would surely imply that administering kynurenine to us is a bad plan..? 😬
 
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Osaca

Senior Member
Messages
344
I always thought, that this statement was also a reflection of the Kynurenine trial, but I might have overinterpreted things.
When the experimental data do not consistently corroborate a theory like the IDO metabolic trap, I'm naturally disappointed. But if you want to do science, you have to be prepared for that disappointment. You have to get back up, think hard, and imagine another theory to test.

This “massive elevation” in IDO2 values is what the news reported and not a reflection of the paper itself, right?

From the paper it seems to me that at least 4 of the non-hospitalized PASC patients (n = 9) had higher levels than 10 of the fully recovered SARS-CoV-2-infected patients (n = 14), based on staining without quantification.

Given its metbolic nature, it would be interesting to see what the results would be if they could include severe LC patients, since all of their patients are still able to partially work and the patients from the MUSCLE-PASC study are at least fit enough for a bike ride test. It seems this study could be quite suitable even for patients that are on the severe end as only a tissue biopsy/blood sample would be required or did I miss something?
 
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ZeroGravitas

Senior Member
Messages
141
Location
UK
this statement was also a reflection of the Kynurenine trial
I don't think I was following closely enough to be sure of the reason... But, yeah, it definitely seemed like drawing a line under the tryp-trap as his most promising possibility.

Although, the yeast experiments seemed to work out fine, the Itaconate Shunt could maybe cause a tryp-trap (via INFa?) and Ron Davis was still talking about the trap as a possibility (to be excluded) at the conference in Cambridge, a couple months ago:

Cropper2023-08-13-00-21-42-1108264.jpg


This “massive elevation” in IDO2 values is what the news reported and not a reflection of the paper itself, right?
They maybe said more about this in their previous paper. Because in this one they recount:
Recently, we showed that the otherwise rarely expressed tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) was abundantly expressed and enzymatically active in lung, heart and brain, and also monocytes and lymphocytes of patients with fatal COVID-19.
But I'd like to discuss that more in the relevant thread. 🙂
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
The problem I see with that research is that ME's mechanism may not show up in serum; it could be a localized abnormality in just part of the brain. I don't get excited about any ME research that's based on serum, or for that matter, parts of the body other than the brain.

I think one of the problems with ME research is the the word "fatigue". Fatigue is poorly defined and poorly understood. I think many (most?) people assume that "feeling fatigued" is physical, therefore the problem lies in the muscles or metabolism. Researchers specializing in those areas will of course approach the problem with that attitude.

I wish someone would do a test to answer the question of where ME's 'fatigue-like' symptom originates. Is it caused by dysfunction in the muscles or metabolism, or is it neurological? Answer that question, and then allocate funding appropriately.
 

almost

Senior Member
Messages
123
I couldn't find any probiotics which contained this. Did you find any? Thanks

Pam
I found two:
Life Extension Bifido GI Balance​
Natural Factors Travel Probiotic​

This looks interesting to me as I have high Kynurenine, higher Quinolenic Acid and low Tryptophan, so lowering the ratio is a goal. I need to check it out further, but interesting . . .
 

almost

Senior Member
Messages
123
I have ordered some BCAAs to see if they improve my PEM when taken at each meal
I'm having a bad PEM day today, and I may finally break down and give this a try. I really don't need to reduce tryptophan I believe, as I already am at about the 34th percentile per NutrEval, and it would then theoretically increase my Kynurenine / Tryptophan ration further. But, I'm in the mood to experiment, so possibly . . .
 

bertiedog

Senior Member
Messages
1,738
Location
South East England, UK
I found two:
Life Extension Bifido GI Balance​
Natural Factors Travel Probiotic​

This looks interesting to me as I have high Kynurenine, higher Quinolenic Acid and low Tryptophan, so lowering the ratio is a goal. I need to check it out further, but interesting . . .
I have ordered the Life Extension one and have a new yoghurt maker which should help. I have read it is much harder to ferment Bifido bacteria as it will need a prebiotic to feed off plus the milk of course. Also it needs to be kept at approximately 39 C for maybe 24 hours depending on the strength of the probiotic used. Also sterilisation of all equipment is very important to ensure no fermentation of bad bacteria. I will boil the organic milk I use and then let it cool to around 39 C before mixing in the prebiotic and probiotics.

Just looked up Biomesight recommendations from my recent stool sample and this probiotic is recommended to help my microbiome!

Good luck with your experiments. Its all trial and error as far as I can see.

Pam
 

almost

Senior Member
Messages
123
Good luck with your experiments. Its all trial and error as far as I can see.
Good luck to you as well. Yes, lots of trial and error, with some success sprinkled in.

Yes, Bifido is said to require higher temps than the Lacto, etc. I have tried it solo with the Yogurt cycle on my InstaPot, and got a nice thick yougurt, so maybe it still works. I'm not in a position to culture it and find for sure. Now I just mix it with the rest I use and go with that.