New update from Prof. Ron Davis on the 'Metabolic Trap' hypothesis

[Ben H]

Hi guys,

I hope everyone is doing as okay as possible.

Here is the latest update from Prof. Ron Davis on the Metabolic trap hypothesis:

Big thanks to Ashley Haugen for her hard work on this, and of course to Ron (and Janet).



B

 

[ljimbo423]

Sounds encouraging so far. At least they haven't ruled it out as the possible cause of ME/CFS. It's just one more area of research that is being looked into. Which I think is a good thing.

 

[Hopeful1976]

I just wish upon wish it would all move with speed. I remember Robert Phair when he initially brought this idea to the open. That was a fair few years ago now. What's happened with the nano needle now? Has that one been abandoned? It seemed so hopeful and in my naivity I believed an answer would come soon. That was 6 years ago.... sorry to be pessimistic, it breaks my heart that our suffering is never ending. No answers. No one still knows what causes this cruel disease.

 

[Ben H]

Sounds encouraging so far. At least they haven't ruled it out as the possible cause of ME/CFS. It's just one more area of research that is being looked into. Which I think is a good thing.

Exactly. As Ron says in the video, they are not looking to prove this, they're looking to disprove it and so far they haven't been able to. Which is good, as far as the hypothesis goes.

I just wish upon wish it would all move with speed. I remember Robert Phair when he initially brought this idea to the open. That was a fair few years ago now. What's happened with the nano needle now? Has that one been abandoned? It seemed so hopeful and in my naivity I believed an answer would come soon. That was 6 years ago.... sorry to be pessimistic, it breaks my heart that our suffering is never ending. No answers. No one still knows what causes this cruel disease.

I agree. The speed/wait is so difficult. The lack of any significant governmental/institutional funding is the real issue. The pandemic also has not helped of course. But they are making progress, and the nanoneedle is still very much part of the research. Many irons in the fire, so to speak.


B

 

[Hopeful1976]

Exactly. As Ron says in the video, they are not looking to prove this, they're looking to disprove it and so far they haven't been able to. Which is good, as far as the hypothesis goes.




I agree. The speed/wait is so difficult. The lack of any significant governmental/institutional funding is the real issue. The pandemic also has not helped of course. But they are making progress, and the nanoneedle is still very much part of the research. Many irons in the fire, so to speak.


B

It's just tough. Being in the uk doesn't help. I am praying every day that I will get just a few years of health, one day

 

[Breagjam]

It's just tough. Being in the uk doesn't help. I am praying every day that I will get just a few years of health, one day

I hear you

 

[junkcrap50]

From reddit, by /u/Calamondinchameleon, a summary of Ron's video.

Summary:
Update on Metabolic Trap Research

• The Robots have been fixed by Angela Chu.

• They are now in the process of screening the FDA approved drugs.

• 1,100 drugs to test and they are about one third through.

• They have found a number of drugs that appear to turn the IDO1 pathway back on in yeast.

• This could be due to other methods. It is possible that the drugs are turning on drug pumps that are removing the tryptophan from the cell.

• This should be easily fixed in yeast. They can even edit the genes of the yeast if necessary.

• They will continue to screen drugs and look for a common feature among them.

• It is likely that these drugs are binding to the IDO1 enzyme and inhibiting enzyme inhibition.

• If they can find commonalities in the drugs that work, it is more likely that it is doing what they want.

• They can also test these drugs on cells in vitro in a test tube, but they also need to test if they will work on human cells.

• They have been working on Macrophages from healthy people’s blood and will soon begin on patient’s blood.

• This is hard to do safely because of Covid-19 and because the blood cannot be freezed before use.

• Preliminary data shows that human cells can be in the metabolic trap.

• They are close to being able to test in vivo.

• Ron is excited, but so far they are trying to disprove the metabolic trap theory as this is the best way to test a theory.

• So far they have not managed to do so.

• They are also looking at other metabolic traps that could be involved in the disease.

 

[Learner1]

@junkcrap50 Thank you for posting! Now, just wish I were a yeast...

Does anyone have a clue of the other metabolic traps?

 

[Reading_Steiner]

Seen many theories come and go, Rituximab comes to mind, forgive me if I feel it won't be such a simple matter to solve the disease, even if we have the best scientist in the field with the most efficient method etc. Yeast is single cell, human have different cells with different specializations that can monitor each other in a big network, maybe only some cell types will remain trapped. Humans have a bacterial colony that might interact with this chemical process, humans can also modify their own environment more than a yeast can, human can change its temperature, perform exercise, consume food or drugs which might interact to break the state. Theres also the factor that some patients on this forum have already tried altering their relevant chemicals to escape the hypothetical trap. I hope this works but i'm not going to get my hopes up as it were.

 

[Oliver3]

Seen many theories come and go, Rituximab comes to mind, forgive me if I feel it won't be such a simple matter to solve the disease, even if we have the best scientist in the field with the most efficient method etc. Yeast is single cell, human have different cells with different specializations that can monitor each other in a big network, maybe only some cell types will remain trapped. Humans have a bacterial colony that might interact with this chemical process, humans can also modify their own environment more than a yeast can, human can change its temperature, perform exercise, consume food or drugs which might interact to break the state. Theres also the factor that some patients on this forum have already tried altering their relevant chemicals to escape the hypothetical trap. I hope this works but i'm not going to get my hopes up as it were.

Good to be cautious.
Also good to have hope tho. And even if this theory gets disproved, other science will be built on its shoulders.
We just gotta hang on in there and appreciate Ron's efforts I feel. And Angela and the rest of the team

 

[elvira]

I’m trying not to get my hopes up, but seeing his updates always make me smile. Ron

 

[Learner1]

Seen many theories come and go, Rituximab comes to mind,

Rituximab has helped many patients. But, doctors must select patients appropriately to use it.

The problem is this is not one homogeneous disease. Each of us has individual genetic and environmental factors and different disease triggers, so it's unlikely the sane single drug will cure us all. Individualized medicine is the way to go.

 

[HealingFalcon]

For those of you with CCI and tethered cord:

https://pubmed.ncbi.nlm.nih.gov/30019623/

I stumbled across this article (I only could read the abstract) which states an altered tryptophan metabolism following traumatic brain injury. Tryptophan seems increased as the serotonin/tryptophan and melatonin/tryptophan ratios are decreased and IDO 1 is increased.

Although only hypothetical, it would fit the metabolic trap hypothesis and might explain ME/CFS following CCI as well as TC.

Chronic TBI (due to structural abnormalities)
-> disturbed tryptophan metabolism (influx of tryptophan?)
-> IDO 1 activity increases
-> continued tryptophan influx
-> substrate inhibition starts and IDO1 stops working
-> metabolic trap

Any thoughts? Who can read the whole paper?

 

[Rufous McKinney]

• Ron is excited, but so far they are trying to disprove the metabolic trap theory as this is the best way to test a theory.

I assume this just means they intend to test a null hypothesis, which is how you do a basic experiment statistically, you attempt to disprove it.

 

[Consul]

I read at another forum that patients have no more mutations in the enzyme in question than does controls. Does not sound great. Anyone have more info on this?

 

[Learner1]

I read at another forum that patients have no more mutations in the enzyme in question than does controls. Does not sound great. Anyone have more info on this?

These are slides from Dr. Phair's initial presentation at Stanford. One of the points he made was he was looking for common mutations. The trap doesn't get triggered just because one has a mutation.

 

[GlassCannonLife]

Just thinking about this - assume that taking one of the drugs Ron recently identified to fix the trap in Yeast would actually resolve ME in us. Doesn't that suggest that out of the many hundreds of drugs we would have taken between all of us, none of them would have been this/these drug(s)?

Unless some people have gotten better and it's (/they've) been lost in a list of things they tried... I feel like we would have noticed this as many people have compiled reports of various responses to drugs and nothing so far has a uniformly beneficial effect in the ME population.

Which again suggests that we simply haven't tried this drug yet..?

Or the more depressing alternative - the same drugs aren't effective in the human condition.. I wonder how soon into human cell trials they'd spill some information about what the leading candidates are (if there are any). I hope they wouldn't just sit on it for months if they are seeing response.

 

[Consul]

@Learner1 Ppl over at s4me claim Ron has acknowledged that there is no difference between patients and controls wrt mutations. In my mind the trap theory rests on (big) mutation prevalence difference between patients and controls.

 

[Learner1]

@Learner1 Ppl over at s4me claim Ron has acknowledged that there is no difference between patients and controls wrt mutations. In my mind the trap theory rests on (big) mutation prevalence difference between patients and controls.

No idea. I think it would be a lot simpler if certain people hadn't decamped to s4ne making conversation difficult.

My own experience is that fixing thee UDI2 metabolic trap doesn't cure ME/CFS

 

[Rufous McKinney]

Doesn't that suggest that out of the many hundreds of drugs we would have taken between all of us, none of them would have been this/these drug(s)?

yeah thats a fairly logical chain of thoughts, unless its really obscure which is possible I suppose.


And I read there are 22,000 FDA drugs so that sounds like alot more than they intend to test currently. So there must be some screening going on.