Ron Davis speech at 14th Invest in ME Research International ME Conference.

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The IDO2 genetic observation is not necessarily tied to the IDO metabolic trap hypothesis, although it does agree with it. The data tells us that a faulty IDO2 is very likely required to develop ME/CFS, along with perhaps some other genes like @Cam Newton mentioned. But that only brings us one step closer to the IDO1 trap theory. It could also be that IDO2 serves some other role that keeps people with a functioning IDO2 from developing ME/CFS, it may not necessarily tie to the trap model of Robert Phair.

One thing that concerns me a bit is how common this IDO2 mutation is. Robert Phair was originally looking for mutations that were not rare (by rare is probably implied something like less than 1% of population), but now we have found a mutation that affects the majority of the population. If 0.5% of the entire population gets ME/CFS, then with 75% having a faulty IDO2, if you belong to the faulty IDO2 group, you still only have a 0.66% likelihood of getting ME/CFS. In other words, a lot that has to go wrong for someone to develop ME/CFS even with a faulty IDO2.

To contrast it with some other disease causing mutations, for example there is a well known BRCA mutation that is tied to breast cancer. It is estimated that a massive 70% of women with BRCA mutation develop breast cancer during their lifetime, as opposed to around 12% in the general population.
Okay we will have to agree to disagree on whether he has good evidence for the trap. As for the mutation being so common and how you say if that's the case a lot would have to go wrong for someone to develop ME/CFS even with the mutation, I agree with that, but that is not an issue in my mind. For example, think about how many underaged, uneducated drinkers there are out there who drink with no knowle
The IDO2 genetic observation is not necessarily tied to the IDO metabolic trap hypothesis, although it does agree with it. The data tells us that a faulty IDO2 is very likely required to develop ME/CFS, along with perhaps some other genes like @Cam Newton mentioned. But that only brings us one step closer to the IDO1 trap theory. It could also be that IDO2 serves some other role that keeps people with a functioning IDO2 from developing ME/CFS, it may not necessarily tie to the trap model of Robert Phair.

One thing that concerns me a bit is how common this IDO2 mutation is. Robert Phair was originally looking for mutations that were not rare (by rare is probably implied something like less than 1% of population), but now we have found a mutation that affects the majority of the population. If 0.5% of the entire population gets ME/CFS, then with 75% having a faulty IDO2, if you belong to the faulty IDO2 group, you still only have a 0.66% likelihood of getting ME/CFS. In other words, a lot that has to go wrong for someone to develop ME/CFS even with a faulty IDO2.

To contrast it with some other disease causing mutations, for example there is a well known BRCA mutation that is tied to breast cancer. It is estimated that a massive 70% of women with BRCA mutation develop breast cancer during their lifetime, as opposed to around 12% in the general population.
For me it just comes down to your word vs Ron Davis' word. I am not trying to insult your intelligence. But certainly nobody on these forums has a level of intelligence anywhere near that of what Ron Davis possess. He has proven to be literally one of the most genius people on earth. I am not saying he is never wrong, but for him, with such intimate knowledge of the suffering these patients go through and how soul shattering it is to them every time a new hope falls through, to say that the theory is, "Probably correct". Just carries a TON of weight for me. Nothing anybody on here could say could ever convince me otherwise.
 

percyval577

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What is the relationship between indoleproprionate and IDO2?
A priori there is none (as I have grasped it). Only that they might have been found to appear regularly in us (if this will hold on), probabaly I think. So then there might show up something, maybe a predisposition for getting thrown into mecfs. The next question then were, how would they both work together that a lack of them could mean a vulnerability.
 
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percyval577

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@bctjr1993? (I don´t understand your message.)

(my paragraphing)
One thing that concerns me a bit is how common this IDO2 mutation is. Robert Phair was originally looking for mutations that were not rare (by rare is probably implied something like less than 1% of population), but now we have found a mutation that affects the majority of the population.

If 0.5% of the entire population gets ME/CFS, then with 75% having a faulty IDO2, if you belong to the faulty IDO2 group, you still only have a 0.66% likelihood of getting ME/CFS. In other words, a lot that has to go wrong for someone to develop ME/CFS even with a faulty IDO2.
I think Phair had the idea that IDO is invovlved because it is that common. And then he had the whole idea (I just lost the brilliancy where everything sticks nicely together).

However, Phair says in his article both, in the introduction: (my paragraphing)
Genetics must hold clues to ME/CFS because, like other chronic diseases, there is evidence that this disease can run in families, but it is clearly not a disease one has at birth.

Rather, there appears to be a genetic propensity that lies hidden until a particular collection of triggering circumstances arises in the patient’s microbial, dietary, micronutrient, physiological, emotional or physical environment.
...
Outbreaks or epidemics of a noncontagious disease raise the possibility that genetic predisposition to ME/CFS is very common in the population and that the disease has low penetrance only because the initiating triggers are multifactorial, and those pathogenic combinations of triggers are, themselves, rare.

Outbreaks are then explained by a geographically localized combination of factors superimposed on a genetic predisposition that is common in the population. Thus, it is the existence of ME/CFS outbreaks that pointed to the potential importance of common damaging mutations.
and also in 4.4: (my paragraphing)
While it is possible that the IDO metabolic trap lays bare the etiology of ME/CFS, the probability that this is so is small.

When we search for common damaging mutations in the human genome, we, by definition, find many. Consequently, the hypothesized increase in damaging alleles in ME/CFS will be difficult to demonstrate without a much larger population of carefully diagnosed ME/CFS patients whose genome sequences are available.
...
The mutation(s) will have low penetrance because it is one or more rare combinations of environmental circumstances that trigger the disease and determines its prevalence. If this is true, the fraction of the world’s population at risk for ME/CFS may be vastly greater than its 2% estimated prevalence of the disease.
 
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Gemini

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At the 17 minutes mark he talks about Copaxone, which he says makes MECFS patient blood "look healthy" (presumably in terms of impedance)
@Murph, excerpts from Wikipedia's Copaxone "Mechanism of Action:"

"Administration of glatiramer acetate shifts the population of T cells from proinflammatory Th1 T-cells to regulatory Th2 T-cells that suppress the inflammatory response.[9]"

"Given its resemblance to myelin basic protein, glatiramer acetate may act as a decoy, diverting an autoimmune response against myelin."

"Studies in animals and in vitro systems suggest that upon its administration, glatiramer acetate-specific regulatory T cells (Tregs) are induced and activated in the periphery, inhibiting the inflammatory reaction to myelin basic protein.[10]"

[my bold]

At the IIME Conference Dr. Fluge expressed interest in Andersson's discovery of autoantibodies in the periphery causing pain in FM, and in Ron's nanoneedle findings in the blood, asking could it be an antibody?

Thread on Andersson's IIME presentation is here:
https://forums.phoenixrising.me/thr...omyalgia-igg-autoantibodies-cause-pain.77229/