Dr Ron Davis - Updates on ME/CFS research - September 2019 onwards

John Mac

John Mac

Senior Member (Voting Rights)
Gene mutation IDO2

Every ME/CFS patient has this mutation.

Biochemists and Geneticists say IDO2 is not necessary, it doesn't have a function.

Clearly not true as every patient has this mutation.

We have hypothesis: No details yet but called 'Metabolic trap'.

We are trying to prove hypothesis wrong which is the right way to go.

One compound that is made in the gut and it appears that the bacteria is missing in the patients and that product is used to protect the brain.

 
Barry said:
Although I know it is not universally agreed, many believe the human appendix has no useful function in modern humans. But everyone has one.
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I heard on a radio documentary that the appendix has evolved on about 30 separate occasions in various species, which would seem to argue against it being a vestigial organ. They were discussing the theory that it may be useful in immune function, and as a repository for digestive bacteria in case essential species get wiped out by disease.

I'd definitely agree with both of you that not understanding the function of something doesn't add up to an argument that it has no function.
 
The metabolic trap.

I don't know, but if in simple terms this means pwME are not metabolizing properly, then this makes sense to me in terms of my experience with testing for heavy metals.

Early on, even with chelators to provoke excretion of metals, very little showed up in my tests.

No, or next to no mercury showed up despite having many mercury fillings.

Other metal results were the same early on - they hardly registered.

One would think I had not been around much in the way of heavy metals ever - in fact I was told that - "heavy metals were not a problem for me."

This was incorrect.

It took many tries with chelators for any mercury, lead, arsenic, cadmium. nickel, aluminum, etc. to show up.

When they finally did, the numbers were very high for several different metals.


Drug chelators should be used under medical supervision, and often times patients' good minerals need to replaced a day or so after the chelation drugs are administered.

I found going through the chelation process increased fatigue - perhaps due to these drugs pulling out things like iron.


I don't know if my heavy metals experience has anything to do with the metabolic trap hypothesis; perhaps just speculation on my part.
 
Barry said:
Just to be pedant. Although I know it is not universally agreed, many believe the human appendix has no useful function in modern humans. But everyone has one.
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I'm usually screaming internally whenever I hear how most of our DNA is junk DNA that serves no purpose because it does not code for proteins. Sometimes it's just "we don't know what it does" but far too often it's declarative assertions that it is useless.

Because the blueprints come out of miasma, I guess. Or the brain's layout and universal functions like edge detection and an innate understanding of how light and shadow should behave.

Great example of what maxing out intelligence gets you when you take the points out of wisdom.
 
rvallee said:
I'm usually screaming internally whenever I hear how most of our DNA is junk DNA that serves no purpose because it does not code for proteins. Sometimes it's just "we don't know what it does" but far too often it's declarative assertions that it is useless.

Because the blueprints come out of miasma, I guess. Or the brain's layout and universal functions like edge detection and an innate understanding of how light and shadow should behave.

Great example of what maxing out intelligence gets you when you take the points out of wisdom.
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Dead code basically. Maybe natural selection is better at adding useful stuff in, than it is at weeding redundant stuff out.
 
DokaGirl said:
The metabolic trap.

I don't know, but if in simple terms this means pwME are not metabolizing properly, then this makes sense to me in terms of my experience with testing for heavy metals.

Early on, even with chelators to provoke excretion of metals, very little showed up in my tests.
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The metabolic trap is simply a name given to a still hypothetical model of tryptophan building up in the cells due to issues with tryptophan to kynurenine conversion caused by a damaged IDO2 gene. That isn't to say there aren't other metabolic problems in ME/CFS, but they are looking for a root cause of all of this havoc and IDO2 issues could prove to be one.

I think Ron Davis has found a way to communicate his message rather well across in these videos. It's just a shame there isn't much groundbreaking news in the last year or so.
 
What does it mean that "every" patient has a mutation for IDO2? How many people? Tested where?

How common is the mutation in people w/o ME/CFS?

What would be involved in getting tested oneself?

It would mean a great deal to me to at least find a marker before I shuffle off the planet.

It has been too damn long. Not sure how much time I have left.

Bill
 
@JES

Thank you for your explanation - it was straight forward and easy to understand.

Although this forum is Science for ME, I think plain language explanations are helpful for some of us with less science background - I have some post-secondary science, but that was not my main focus. Following the intricate science gets complicated at times, so I appreciate your comments.


Thanks again. :)
 
Bill said:
What does it mean that "every" patient has a mutation for IDO2? How many people? Tested where?
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He's referring to a specific study – the Severely Ill Big Data study – not literally everyone with ME.

Bill said:
How common is the mutation in people w/o ME/CFS?
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Very common, more than 50% of people are likely to have them. They've never suggested that IDO2 mutations are in any way causative of ME, just that they could predispose to it. If the theory is correct, it relies on an uncommon trigger, not an uncommon mutation. It's possible the trigger relies on two or more factors (such as immune insults from viruses, extreme stress, etc) occurring simultaneously or close together in time.

Bill said:
What would be involved in getting tested oneself?
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Direct-to-consumer genetic testing, such as 23andMe, will show up some of the mutations; or whole genome sequencing, such as Dante Labs. Unless you want to do it for some other reason, it's unlikely to be helpful to you at the moment. These SNPs are so common that they're not diagnostic, and the theory could be wrong anyway.
 
Bill said:
the hope that an IDO2 mutation will somehow serve as a marker for ME/CFS.
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I don't think anyone's ever said that, as something so common couldn't possibly be a useful marker. What they're saying is that it's part of a theory of how ME is triggered and perpetuated.

The next job is to try to disprove this theory; if they can't do so, then it begins to look much more robust.
 
Kitty said:
I don't think anyone's ever said that, as something so common couldn't possibly be a useful marker. What they're saying is that it's part of a theory of how ME is triggered and perpetuated.

The next job is to try to disprove this theory; if they can't do so, then it begins to look much more robust.
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How big was the cohort? The small difference between the control group and the patient could be due to the small sample size.
And even if the cohorts are big enough, is the difference (98% patients, 90% control) big enough to tell us anything?
 
Kitty said:
I don't think anyone's ever said that, as something so common couldn't possibly be a useful marker. What they're saying is that it's part of a theory of how ME is triggered and perpetuated.

The next job is to try to disprove this theory; if they can't do so, then it begins to look much more robust.
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Ron Davis' video linked above offered zero context about how common the IDO2 mutation might be.

Further, he seems to suggest that ALL ME/CFS patients carry the mutation as if this is a significant finding and it is the finding that seems to drive his hypothesis.

Without including a reasonable context for the distribution of this mutation, I find the video irresponsible. IMO it raises false hopes.

Bill
 
Cheshire said:
And even if the cohorts are big enough, is the difference (98% patients, 90% control) big enough to tell us anything?
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No, not if the proposition is that an IDO2 mutation is causative of ME. But Dr Phair, who developed the theory, has been clear that it isn't causative.

If the theory's correct – and that's still a big 'if' – it's simply a vulnerability that won't affect the majority of people who have it. It only impacts the very small minority who experience a particular trigger or collection of triggers at a critical time.

Bill said:
Without including a reasonable context for the distribution of this mutation, I find the video irresponsible.
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This is a fair point, but it's part of a series of video presentations at a number of events where the background to their work has been made clear. Through these films, Dr Davis is trying to keep up the morale of people who've been waiting decades for some good news – and it absolutely is good news, because it's good science. The theory might be completely wrong; but if it is, they'll say so openly and promptly. For people like me, ill for nearly 45 years, that alone is immensely hopeful.

ETA: words 'an' and 'mutation' added for clarity.
 
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