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Ron Davis Update

JES

Senior Member
Messages
1,323
They still need to publish or at least present their failed experiments and data that refutes their many hypotheses they hype up and spread via interviews and other media.
I have a feeling that most of the metabolic trap work was related to Phair's mathematical model and simulations. In other words, it was at sort of alpha hypothesis stage. They should publish more, but I think the likelihood of it being correct was overhyped.

Some more questions I'd like to get answered related to it still. They found something like 69 out of 70 of the severe patients they looked at had one or several mutations somewhere in the IDO2 gene rendering it non-functional. I wonder if they did further analysis of this including more patients so that it was more statistically significant.

The other thing they mentioned I reckon a year or two ago was that the metabolic trap had been replicated in yeast cells, but I'm wondering if something in those experiments later on disproved this model.
 

junkcrap50

Senior Member
Messages
1,334
The other thing they mentioned I reckon a year or two ago was that the metabolic trap had been replicated in yeast cells, but I'm wondering if something in those experiments later on disproved this model.
Probably, and yeah it was a very early hypothesis. Nevertheless, they still ought to release the info letting people know it was disproven or less likely probable. But the metabolic trap hypothesis did lead to the idea of/creation of the Itaconate Shunt Hypothesis.

Did they not have 2 yeast experiments going on? One with IDO genetically null yeast, or somehow genetically modified, trying to find a substance that releases the substrate inhibition trap & metabolizes the kynurenine. And did they not have a different yeast experiment going on, where they were trying to find (by going through all medications & substances known using a robot) a substance that normalized CFS serum bathed yeast cell's metabolism/ATP - aka countering or reversing the "something in the blood."
 

lenora

Senior Member
Messages
4,926
Thanks @Dude for making sure we saw this report. Also, Dr. Davis, we owe you a huge debt, and I hope you realize that so many of us are grateful to you and your family.

I know that Whitney is a very ill man, but having a father like you, and a mother like Janet Dafoe, and the rest of your family, must help ease his tired mind.

I'll look up the shunt again in order to understand it to the best of my ability. The only people capable of understanding this process would be you, your team and other researchers. The rest of us will try very hard.

You have put in years of your lives, and I would like to say have a nice vacation and don't forget to send us a postcard, but I know that most likely won't happen. Again, thank you. Yours, Lenora
 
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junkcrap50

Senior Member
Messages
1,334
https://www.nature.com/articles/s42255-022-00577-x
Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor.

42255_2022_577_Figa_HTML.png

However, safety of exogenous citraconate is unknown. The Itacondate pathways itself is not fully known as Dr. Davis mentions in the end.
 

Alvin2

The good news is patients don't die the bad news..
Messages
3,024
I recently got a bottle of Malic Acid which would not be affected by this in theory, it does something but its not amazing.
That said i have no idea what dose would be needed, maybe if i took the whole bottle at once?
 

leokitten

Senior Member
Messages
1,595
Location
U.S.
What are thoughts on testing type I interferon inhibitor therapy in ME like is done in SLE? Since they’ve found similar levels of increased IFNa in ME as in SLE. Type I interferon (which includes IFNa) is activated in more than 50% of SLE patients and is considered an important pathogenic factor. There is at least one existing approved drug anifrolumab (Saphnelo) which is a anti-IFNa receptor monoclonal antibody. @Janet Dafoe @HTester
 

leokitten

Senior Member
Messages
1,595
Location
U.S.
And sorry if this idea has already been hashed out and isn’t relevant, but how about clinically testing IL-1 inhibition in ME/CFS patients as proof of concept to see if illness symptoms are indeed driven by inflammation or not? This would circumvent the issue found with testing corticosteroids because of their confounding neuropsychiatric effects
 

hapl808

Senior Member
Messages
2,117
I tried Picamilon which can cross the blood brain barrier and is cleaved to GABA, didn't help my cognitive functioning.

Did you find any benefit from picamilon? Just stumbled across it elsewhere and searched here on PR for a mention of it. Never heard of it before.
 

Alvin2

The good news is patients don't die the bad news..
Messages
3,024
Did you find any benefit from picamilon? Just stumbled across it elsewhere and searched here on PR for a mention of it. Never heard of it before.
Nope, just made it a bit harder to think straight, as if i had taken a very small dose of a sleeping pill.