Scientist Ron Davis Interviewed by WBUR in Massachussetts (6 minute 23 of Q&A)

perrier

Senior Member
Messages
1,082
Likes
2,279
Hi perrier- is this what you are thinking of?

https://www.healthrising.org/blog/2018/04/03/a-metabolic-trap-for-chronic-fatigue-syndrome-me-cfs/



Both good points. For those of us that can tolerate supplements. Hopefully they can give us some insight on how to better target the "circuit".

For those that can't tolerate supplements, maybe they could be helped through some type of diet change? There has to be something that can help those that can't tolerate supplements, I hope.

Jim
Yes, Jim, thanks for finding the statements. This suggests to me, however, that it will be more high powered than the sorts of things patients do now, moderating their diet, and taking support supplements.

What puzzles me is how can addressing a circuit issue deal with the plethora of symptoms and problems patients have: hormone problems, low NK, GI dysbiosis, cognitive issues, memory problems, sleep disorder, toxic feeling, Marconi infections, SIBO, etc. etc.

I do wish we could know more.
 

alkt

Senior Member
Messages
339
Likes
684
Location
uk
when dr davis says there may be no need to develop new drugs . I think he means there are already enough drugs out there that can be used to alter these damaged circuits . since there are already multiple dietary protocols with supplements that have been ineffective in altering the state of m e .
 

ljimbo423

Senior Member
Messages
3,867
Likes
9,710
Location
United States, New Hampshire
What puzzles me is how can addressing a circuit issue deal with the plethora of symptoms and problems patients have: hormone problems, low NK, GI dysbiosis, cognitive issues, memory problems, sleep disorder, toxic feeling, Marconi infections, SIBO, etc. etc.
I'm not certain what Ron is referring to when he calls it a "circuit". If it's some kind of mitochondrial trap or circuit. From the research I've done, dysfunctional mitochondria can cause high levels of oxidative stress AND even immune system activation.

Which could cause a whole host of problems. That could explain, not all but many symptoms.

Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969.

Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system.

The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS.

Sources of continuous activation of O&NS and immuneinflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels.
http://www.eurekaselect.com/118208/article

ETA-
The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease.

Jim
 

pibee

Senior Member
Messages
304
Likes
474
I have a good feeling about this too, which is rare.


Also, I ran into this and it seems to me it could be relevant to the whole 'metabolic trap', especially parts about how ADP levels inside mitochondria are directing pace of energy spending, but if there is some outside chemical like glutamate & pyruvate (commonly used suppements in extreme sports) would influence the spending (bypass ADP levels who control the pace).
And once total sum of ATP+ADP+AMP inside mitochondria is depleted it cant be reversed.
This fits to what they gave us hints in Cort's article.

(Could be totally off since I barely understand what mitochondria does, for now :p)
https://www.researchgate.net/post/W...ucleotide_ATP_ADP_AMP_content_of_mitochondria


Dr Phair:
What controls the total adenine nucleotide (ATP + ADP + AMP) content of mitochondria?
We often discuss the importance of the mitochondrial adenine nucleotide exchanger; indeed, many suggest it is rate limiting for oxidative phosphorylation. But its function has no effect on total mitochondrial nucleotide content.
What is your view of the control of total mitochondrial adenine nucleotide content (ATP + ADP + AMP)? Are isolated mitochondria capable of purine biosynthesis?
If mitochondria can only exchange one mitochondrial ATP for one cytosolic ADP, then there is nothing a mitochondrion can do to increase or decrease the sum of mitochondrial ATP+ADP+AMP. This seems paradoxical. Where does a mitochondrion get its initial allocation of adenine nucleotides?


I also very much doubt they're speaking about commonly used oral supplements because I'd guess way too many people tried so many combos and by now we'd notice big pattern.
It's either high dose IV or something oral high dose that nobody would think of using.
 
Last edited:
Messages
1,505
Likes
7,669
"Because that would possibly mean that we don't have to develop a drug. There may be ways to manipulate that central circuit to get people out of the disease."

how would the central circuit be manipulated?
I wonder how this fits with Naviaux's theory that we need to "flip the switch," to reprogram metabolism. Naviaux had two prior steps: "remove the trigger and refill the tanks." Perhaps this new theory involves some tank-filling too. I'd be surprised if it didn't require certain nutrients or elements in certain orders to get things going again properly, as in refeeding syndrome (itself a kind of metabolic trap, and a fatal one.)

I'm hopeful at the moment, and I'm pleased they're looking at this, but my hope doesn't come mostly from this hypothesis.

This hypothesis seems like looking for your lost wallet in your pockets. It's a good spot to start looking because it's easy to check and if you're right it provides an easy solution. But it doesn't mean it's certain to be where you find it.

My hope comes more from the fact we're now looking for the metaphorical wallet in lots of places at once. No one scientist is very likely to find the answers, but the more of them we have and the more money they have to use, the higher the chance someone will come across something important.
 
Messages
3,299
Likes
4,086
Location
Vermont, school in Western MA
I'm not certain what Ron is referring to when he calls it a "circuit". If it's some kind of mitochondrial trap or circuit. From the research I've done, dysfunctional mitochondria can cause high levels of oxidative stress AND even immune system activation.

Which could cause a whole host of problems. That could explain, not all but many symptoms.

http://www.eurekaselect.com/118208/article

ETA-


Jim
I think CFS is more likely to involve "reductive stress" than "oxidative stress"
 

raghav

Senior Member
Messages
789
Likes
1,801
Location
India
Can they try disrupting this control circuit in lab animals and see whether CFS sets in them and then resetting this control circuit back and see whether the animal returns to normal. This has two benefits. 1) they have lab animal model for cfs and 2) they can confirm that the hypothesis works. I hope they too are thinking along these lines.
 
Messages
1,505
Likes
7,669
Can they try disrupting this control circuit in lab animals and see whether CFS sets in them and then resetting this control circuit back and see whether the animal returns to normal. This has two benefits. 1) they have lab animal model for cfs and 2) they can confirm that the hypothesis works. I hope they too are thinking along these lines.
I think they are doing it in cells first, using patients white blood cells.

Taking it from there all the way to human trials would be a big leap though. Animal trials make sense but I believe they are hard to do - expensive, cumbersome, need ethical approval and results dont' necessarily apply...

How they'd bridge from work in cells to treating patients is a good question. I guess a small pilot trial?
 

Neunistiva

Senior Member
Messages
434
Likes
2,217
Can they try disrupting this control circuit in lab animals and see whether CFS sets in them and then resetting this control circuit back and see whether the animal returns to normal. This has two benefits. 1) they have lab animal model for cfs and 2) they can confirm that the hypothesis works. I hope they too are thinking along these lines.
They can hardly diagnose ME/CFS in humans who can explain their experience in great detail, I have no idea how we would ask rats and mice if they feel like they crashed.

Also, all lab animals differ significantly in their size from humans, which makes their metabolic rate quite different. Since we know metabolism is important in ME/CFS this could skew the results quite a bit.

Very few treatments that work in lab animals translate to humans in general. There's a joke that if you get cancer you'd better be a mouse because then we know how to treat you for sure.

I guess I'm saying all this because I'm severely ill and don't have a few decades to wait while treatment after treatment that worked in rodents fails in humans.
 

caledonia

Senior Member
Messages
4,535
Likes
3,808
Location
Where the land is hilly and they eat hot chili
"Because that would possibly mean that we don't have to develop a drug. There may be ways to manipulate that central circuit to get people out of the disease."

how would the central circuit be manipulated?
The way this is worded could imply either that the circuit can be manipulated without drugs, or that existing drugs could work, and they may not need to develop a new drug. So - kind of ambiguous.

Also, the way he and Naviaux are speaking, using electrical terms like "circuit" or "flipping a switch", maybe they literally mean manipulating the body via electric and/or magnetic fields. Or that could just be an analogy.

So basically, it's as clear as mud. :confused:

But on the bright side, having results on one of the four aspects by the end of summer sounds pretty definite.
 

raghav

Senior Member
Messages
789
Likes
1,801
Location
India
They can hardly diagnose ME/CFS in humans who can explain their experience in great detail, I have no idea how we would ask rats and mice if they feel like they crashed.

Also, all lab animals differ significantly in their size from humans, which makes their metabolic rate quite different. Since we know metabolism is important in ME/CFS this could skew the results quite a bit.

Very few treatments that work in lab animals translate to humans in general. There's a joke that if you get cancer you'd better be a mouse because then we know how to treat you for sure.

I guess I'm saying all this because I'm severely ill and don't have a few decades to wait while treatment after treatment that worked in rodents fails in humans.
Yes you can check lab animals for PEM by making them take the treadmill test (I think it is kind of a wheel inside which the mouse is made to run at a particular speed for particular time. This is used in testing depression in lab mice. They can also look for the low metabolomic profile in the blood. You will be surprised to know the sophisticated testing they do on mice and rats. For this they have different species of rats for different disease models.
 
Messages
45
Likes
76
Location
Netherlands
I think a form of stemcell therapy.

I read a research article about stemcell therapy helps to heal mitochondria in mice... maybe through this centeral control circuit.

So taking your own stemcells... and filter the best ones and inject via IV.

A one time solution..

In this article other solutions are proposed for mito diseases..:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892756/
 
Last edited:

valentinelynx

Senior Member
Messages
1,271
Likes
3,337
Location
Tucson
I'm wondering what other serious diseases can be cured simply by "manipulating circuits", because I can't think of any.
What comes to my mind is the large set of congenital illnesses called "inborn errors of metabolism"

As defined by Wikipedia: "Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of metabolism.[1] ... In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds."

Some of these disorders, which are often quite serious, life-threatening in early life, are treatable with dietary modifications, supplements or vitamins.

Also, you might say that Type 2 diabetes is treated by "manipulating circuits": to a large extent it can be treated by dietary modification, not overloading the carbohydrate (sugar) processing system/circuit.

And there's gout, in which too much uric acid in the blood can lead to deposition of uric acid crystals in joints. Treated with dietary changes to reduce the amount of purine production because purine metabolism leads to uric acid production. Modifying the "circuit" of purine production through dietary change reduces uric acid production and decreases gout attacks.

Of course, diabetes and gout are often also treated with medications, but medications are not always necessary, if the body's "circuits" can be tweaked adequately with diet or other means.

I'm sure there are even better examples, but that's what comes off the top of my mind. Not sure if this is the sort of thing that Dr. Davis & co. have in mind, either?
 

Riley

Senior Member
Messages
169
Likes
428
If I remember correctly, only about 10 patients and 10 controls have been tested so far. Only one member of Dr. Davis' team knew how to make them properly so instead of making new ones they resorted to cleaning the existing ones. And then our blood started getting stuck in the needles which became a clue that our red blood cells might not be as elastic as they're supposed to be.

Also for something to become a diagnostic test it needs to go to rigorous rounds of scientific research, NIH approval and then adoption in every lab around the world. Can you imagine how long that takes?
I'm curious about this as well. They've been talking about the nano needle for what, two years now? It sounds like a home run. How is it possible they've only run it on 10 patients?

I say this with all due respect to Dr. Davis and OMF, and I'm sure there are reasons, but as someone following developments from the outside it is puzzling.