A Metabolic Trap for ME/CFS?

[Sundancer]

I have no idea why you think "by now ... should have completed .... xyz". They are working on it.

I have full trust that Ron and his team will go to the deepest end to find answers that are rigorously statistically underpinned. Whatever time and effort it may take.

That will take time, research takes time, good research takes more time, this is a very hard nut to crack and hearing they have made a dent and a small crack in the nut leaves me comforted. As I am sure they will not come out with things that they are not very sure off.

They are working on it, and I'm grateful, for the workers, and for those people that donate money to make it possible. Also grateful that those things they are sure of, or that are real hopeful, get told to the patients. Instead of only knowing that somewhere, some team is doing something you have no idea about.

In the meantime I'll go on trying to take as good care of my body as I can.

love for you, Ron and Whitney

 

[raghav]

The reason why I said "By now they should have completed Proof of concept Testing" is from the three statements mentioned in the OMF newsletter attributed to Dr. Ron Davis, which are
1) We are quite sure the treatment will take only a few days.
2) It will be a one time treatment.
3) It will be relatively inexpensive

If you analyze these three statements you will see that they have found what the cause is and they also know what the treatment (compound or chemical) is going to be. That is the reason I said "They Should".

 

[valentinelynx]

The reason why I said "By now they should have completed Proof of concept Testing" is from the three statements mentioned in the OMF newsletter attributed to Dr. Ron Davis, which are
1) We are quite sure the treatment will take only a few days.
2) It will be a one time treatment.
3) It will be relatively inexpensive

If you analyze these three statements you will see that they have found what the cause is and they also know what the treatment (compound or chemical) is going to be. That is the reason I said "They Should".

The communication from Dr. Davis that I read, called, "A Glimpse into Dr. Ron Davis’ Talk in London" said the following:

"We are conducting system biology and pathway analysis that shows that a metabolic trap is possible, and that some of the observed mutations make it more likely. If this is the case we should be able to push the patients out of this state by a specific metabolic intervention. We are very hopeful that this could be a one time treatment, take only a few days, and be relatively inexpensive.” [The emphasis is mine]​

Dr. Davis is stating his high hopes that a particular hypothesis regarding the etiology of this illness will pan out, and if it does, then the statements you quote will then apply.

If there is another place where he made these statements unequivocally, I haven't seen it. Of course, I really, really want the metabolic trap hypothesis to be correct, and that Dr. Davis to be right that this hypothesis will lead to a readily accessible, rapid, permanent and 100% effective treatment. Can you imagine? I barely can!

But the work still needs to be done, the hypothesis must be tested, and if they do indeed find a metabolic trap, then they must find and test treatment options.

High hopes, indeed! Which can be very scary... Good luck and Godspeed to Dr. Davis and colleagues!

 

[FMMM1]

The reason why I said "By now they should have completed Proof of concept Testing" is from the three statements mentioned in the OMF newsletter attributed to Dr. Ron Davis, which are
1) We are quite sure the treatment will take only a few days.
2) It will be a one time treatment.
3) It will be relatively inexpensive

If you analyze these three statements you will see that they have found what the cause is and they also know what the treatment (compound or chemical) is going to be. That is the reason I said "They Should".

I was a science technician a long time ago.

I once worked with a young student who was doing a PhD on B12 in sheep. The student noticed that the sheep fed a diet with insufficient cobalt couldn't produce propionate but instead produced succinate. It was a workaround i.e. the sheep used succinate instead of propionate as there energy source.

I'm guessing the following. These guys (Phair, Ron Davis and others) are going to test whether those with this genetic defect can convert X to Y i.e. whether the normal metabolic pathway exists. Since they know that those with the genetic defect generally have a work around they'll presumably look for evidence of this e.g. can they convert X to Z to Y (same outcome different route).

In order to do this you need labelled (stable isotope) copies of X, Y, Z ---; if your lucky then you can buy copies of these. You also need the equipment to test samples high resolution mass spectrometry I'm guessing (0.5 million dollars for the spectromer?) and the folks to run this equipment. Phair's project will have to be managed with competing projects in what is after all a commercial venture.

I am also frustrated/despair; how can something relatively basic not be delivered? I.e. how come we don't have systems in place to fund research to try to resolve these problems so that those with ME/CFS have the potential to be diagnosed and treated? I donated a few dollars to OMF; however, those working on something this important should have access to public funds.

I think a positive here is that we seem to be getting access to the best scientists e.g. Phair and Ron Davis. Also, they realised the need to bring in other scientists e.g. Melbourne, Utah, Cornell ----. What they are trying to figure out is extremely complex.The kit (mass spectrometry etc) is one thing but the key ingredient are the scientists. Another positive are those like Jennifer Brea and Cort Johnson who have raised the profile of this illness.

I share your frustration but I feel it needs to be directed to securing political support for funding for research, and the delivery of diagnostic tests and treatments, once we understand the disease.

Here's hoping they progress our understanding so that those whose lives have been impacted can be diagnosed and treated.

 

[Aroa]

It would be great to have Robert Phair at the next Stanford Symposium

 

[J.G]

I once worked with a young student who was doing a PhD on B12 in sheep. The student noticed that the sheep fed a diet with insufficient cobalt couldn't produce propionate but instead produced succinate. It was a workaround i.e. the sheep used succinate instead of propionate as there energy source.

I'm guessing the following. These guys (Phair, Ron Davis and others) are going to test whether those with this genetic defect can convert X to Y i.e. whether the normal metabolic pathway exists. Since they know that those with the genetic defect generally have a work around they'll presumably look for evidence of this e.g. can they convert X to Z to Y (same outcome different route).

Thanks, this got me thinking. Somehow I always figured we are dealing with a singular blockade closing off all metabolic pathways downstream of it. A massive boulder that's blocking the motorway, if you like. I never considered the possibility that multiple smaller obstructions, caused by a combination of genetic defects and environmental factors, might have the same effect - or at a minimum, make it impossible to skirt around the boulder using the hard shoulder / slip roads, to continue the analogy.

 

[bthompsonjr1993]

The reason why I said "By now they should have completed Proof of concept Testing" is from the three statements mentioned in the OMF newsletter attributed to Dr. Ron Davis, which are
1) We are quite sure the treatment will take only a few days.
2) It will be a one time treatment.
3) It will be relatively inexpensive

If you analyze these three statements you will see that they have found what the cause is and they also know what the treatment (compound or chemical) is going to be. That is the reason I said "They Should".

You misunderstand those statements.

IF the theory is correct, then those statements will be true. But they have to find out if the theory is correct first, and that will take all summer.

They are not willing to try the treatment until they know if the theory is correct, because they have said that if the theory is not correct, then the proposed treatment could actually cause harm.

 

[perrier]

Hello folks,
Is there anyone out there who would be able to take the time (briefly) to explain exactly what Dr Davis and Dr Phair are presently testing or looking at, in order to determine if their thesis is correct.

In plain English: what tests are they performing? And after the result, how will it be applicable to human? Or will it?
Thank you.

 

[Sushi]

Is there anyone out there who would be able to take the time (briefly) to explain exactly what Dr Davis and Dr Phair are presently testing or looking at, in order to determine if their thesis is correct.

In plain English: what tests are they performing? And after the result, how will it be applicable to human? Or will it?

Have you had a look here? https://forums.phoenixrising.me/ind...orts-article-brief-funding-explanation.60547/

And yes, it will be applicable to humans!

 

[Neunistiva]

@Sushi I think you accidentally linked to the wrong thread. The NIH grant is for Dr. Ron Davis and Dr. Mark Davis to look at T-cells and immunology, that's different than Dr. Phair's metabolic trap and a donation of $1 million from an anonymous donor.

 

[Sushi]

I think you accidentally linked to the wrong thread. The NIH grant is for Dr. Ron Davis and Dr. Mark Davis to look at T-cells and immunology, that's different than Dr. Phair's metabolic trap and a donation of $1 million from an anonymous donor.

Right, I was just thinking of Dr. Davis's part!

 

[perrier]

Yes, thank you, I have been following the immune issue, but I am specifically interested in how they are testing and what to determine the metabolic trap.

 

[wigglethemouse]

@perrier did you see post #151 where @FMMM1 gave a theoretical test example

PDK enzyme was the subject of discussion; lets say it converts X to Y. I guess what they'd do is label the substrate "X" (i.e.label with carbon 14 or similar - stable isotope - mass spectrometer), add this labelled substrate to live cells from someone with ME/CFS, and look at look at what happens to the labelled substrate (carbon 14 or similar). If it isn't converted in the usual way (to Y), or if the rate of conversion is low, then you'd suspect a problem.

I've seen a similar explanation described elsewhere but I can't find it again.....

EDIT : Found it - it's post #184 above also by @FMMM1.

I'm guessing the following. These guys (Phair, Ron Davis and others) are going to test whether those with this genetic defect can convert X to Y i.e. whether the normal metabolic pathway exists. Since they know that those with the genetic defect generally have a work around they'll presumably look for evidence of this e.g. can they convert X to Z to Y (same outcome different route).

In order to do this you need labelled (stable isotope) copies of X, Y, Z ---; if your lucky then you can buy copies of these. You also need the equipment to test samples high resolution mass spectrometry I'm guessing (0.5 million dollars for the spectromer?) and the folks to run this equipment.

 

[wigglethemouse]

@perrier Here is OMF describing the experiment which is similar to @FMMM1 above

During this project, the team will test how cells with these mutations carry out the relevant metabolic reactions, using special ‘tracer’ metabolites that can be easily followed as they are processed by the cells. These experiments will determine whether the mutations are indeed creating a metabolic ‘trap’ that could lead to the neurological and/or immunological symptoms of ME/CFS.

LINK

 

[perrier]

@perrier Here is OMF describing the experiment which is similar to @FMMM1 above

LINK

Brilliant work Wigglethemouse, brilliant thank you.

So, I guess in 2 months we will learn if this thesis holds water. Then, what? Testing on animals? Humans?

Gosh, everyone here needs to really finally win the jackpot.

 

[MonkeyMan]

Brilliant work Wigglethemouse, brilliant thank you.

So, I guess in 2 months we will learn if this thesis holds water. Then, what? Testing on animals? Humans?

Gosh, everyone here needs to really finally win the jackpot.

Yes, except 3 months ... Dr Davis said end of summer.

 

[wigglethemouse]

Yes, except 3 months ... Dr Davis said end of summer.

As someone mentioned earlier in the thread this type of research does not follow a defined timeline like in an engineering project - there are too many unknowns and unexpected twists and turns, and it's likely this project will be no different. I'm hoping we will hear more on the OMF projects at the Symposium on Sep 29
https://www.omf.ngo/community-symposium-2/

 

[anni66]

Thanks, this got me thinking. Somehow I always figured we are dealing with a singular blockade closing off all metabolic pathways downstream of it. A massive boulder that's blocking the motorway, if you like. I never considered the possibility that multiple smaller obstructions, caused by a combination of genetic defects and environmental factors, might have the same effect - or at a minimum, make it impossible to skirt around the boulder using the hard shoulder / slip roads, to continue the analogy.

I think that' s why this illness is so hard to crack.
There is a mechanism which gets everyone to same variety of states but is not homogenous- to me the simplest explanation is a combination of things , including multiple genes and environment.
It also explains the complexity

 

[nryanh94]

@Janet Dafoe (Rose49) do you know if Ron and the others believe with this Hypothesis, that if the metabolic trap is fixed would it also cure those of us who have developed POTS and Mast cell issues along with our CFS?

 

[bthompsonjr1993]

Listen to this video from 4:12 - 4:28, he gives some insight into the immune activation aspect of Robert Phair's theory.

https://www.facebook.com/OpenMedicineFoundation/videos/1524093601028389/