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Ron Davis Update

BrightCandle

Senior Member
Messages
1,133
Based on this theory a IFNa or JAK-STAT blocking drug as often used in cancer for a few days might be enough to stop the cycle of IFNa and recover from the condition, potentially. However if its more complex due to HHV-6 causing continuous activation or a cellular DNA damage then it wouldn't be and I have no idea what you would do in either of those cases since we can eradicate HHV6 in the body and it could be any one of the 100 different internal cellular pathways responsible for keeping the IFNa flowing. Its an interesting hypothesis and it defintely explains everything especially the glutamate and ammonia end of things but its either really close to delivering us a treatment or really far if its correct.
 

Murph

:)
Messages
1,792
Based on this theory a IFNa or JAK-STAT blocking drug as often used in cancer for a few days might be enough to stop the cycle of IFNa and recover from the condition, potentially. However if its more complex due to HHV-6 causing continuous activation or a cellular DNA damage then it wouldn't be and I have no idea what you would do in either of those cases since we can eradicate HHV6 in the body and it could be any one of the 100 different internal cellular pathways responsible for keeping the IFNa flowing. Its an interesting hypothesis and it defintely explains everything especially the glutamate and ammonia end of things but its either really close to delivering us a treatment or really far if its correct.

Phair started off with the idea of a "trap" or positive feedback loop but now he has neither theoretical support for it, nor evidence for it. So the idea taking the drug for 3 days would give permanent relief seems overly hopeful.

His theory now seems to be: the itaconate shunt is downstream of the innate immune system. And something is keeping that innate immune system on. I find this convincing but it's waaaaay less neat and easy to handle than the bistability stuff everyone was so excited about, where you just pop back to full health
 
Messages
600
Im thinking there could be a benefit in keeping a high level of vitamin b5 to alleviate the problem of itaconate stealing all the CoA inside the cells. This is part of why the citric acid cycle doesnt run properly according to Phair.

Lipkin, Hornig 2018 found less fatigue was associated with higher levels of this vitamin.

Sounds like supportive evidence of the theory. I have earlier highlighted this finding in the relevant thread if anyone wants to look it up.
 

Oliver3

Senior Member
Messages
839
Im thinking there could be a benefit in keeping a high level of vitamin b5 to alleviate the problem of itaconate stealing all the CoA inside the cells. This is part of why the citric acid cycle doesnt run properly according to Phair.

Lipkin, Hornig 2018 found less fatigue was associated with higher levels of this vitamin.

Sounds like supportive evidence of the theory. I have earlier highlighted this finding in the relevant thread if anyone wants to look it up.
I can concur about bvits helping. Im part of a B12 deficiency protocol on Facebook.
I haven't implemented the full protocol due to cognition problems but after struggling initially with adrenaline rushes ( acknowledged as part of the protocol) , I use piriton and beta blockers and my energy is better. I don't want to rock the boat, so don't wanna start the whole protocol yet. But it's deffo improved me.
At much higher does people have had full remission from CFS in the group
 

BrightCandle

Senior Member
Messages
1,133
Phair started off with the idea of a "trap" or positive feedback loop but now he has neither theoretical support for it, nor evidence for it. So the idea taking the drug for 3 days would give permanent relief seems overly hopeful.

His theory now seems to be: the itaconate shunt is downstream of the innate immune system. And something is keeping that innate immune system on. I find this convincing but it's waaaaay less neat and easy to handle than the bistability stuff everyone was so excited about, where you just pop back to full health

Yes the simple treatment window is definitely closing now. I would have expected we would find JAK-STAT and IFNa antibodies to have worked in more people accidentally in the past decades if it was that simple. Its looking like its more immune function related. Its a shame really a simple solution with existing approved drugs would have been fantastic but we are now more looking towards trying to eradicate viruses and that is beyond our current technology.
 

lenora

Senior Member
Messages
4,857
As per usual, it seems that things end in a big ?. Someday, though, it will happen. Have hope. Yours, Lenora
 

leokitten

Senior Member
Messages
1,541
Location
U.S.
@Janet Dafoe and @HTester thank you for this excellent talk, it was really well presented and you made it easy to understand while still delving into the metabolism and immunology details.

After seeing both parts yesterday two burning questions

1) In relation to this hypothesis do you have any thoughts as to the possible causes of why some people fall into ME (or LC) while others don’t? This might also help because if this hypothesis turns out to be true even after you correct it with short-term JAK-STAT or IFNa inhibitors we could be more at risk of falling back into ME again.

2) It’s still not clear to me the connection you made showing how cells adjacent to the triggering infection infected cells are hypothesized to be what have a broken metabolism driving ME yet how this illness seems to really badly affect the brain and neurological function. Are you saying that pwME and LC our triggering infection somehow got into the brain or at least caused an immune response in the brain?
 
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Messages
53
Yes the simple treatment window is definitely closing now. I would have expected we would find JAK-STAT and IFNa antibodies to have worked in more people accidentally in the past decades if it was that simple. Its looking like its more immune function related. Its a shame really a simple solution with existing approved drugs would have been fantastic but we are now more looking towards trying to eradicate viruses and that is beyond our current technology.

I wonder what he means by IFNa antibodies, PEGASYS maybe?

In any case, those two classes of drugs are used for Rheumatoid Arthritis and Hepatitis C respectively, and those conditions carry major fatigue with them. So if these drugs helped, people would not necessary make a connectrion to CFS, they wouldn't have had that diagnosis in the first place. Just thinking out loud.
 
Messages
180
One thing irritates me: This whole positive feedback loop can only exist, because somewhere a checkpoint doesn't work, and keeps on not working. So, why then, when we interrupt the feedback loop, would this checkpoint suddenly work again afterwards? Because otherwise the next viral infection, the next inducing of IFN-alpha would bring us right back into the feedback loop, wouldn't it? That would mean, one had to fix that checkpoint, be it by killing off viruses or whatever else is broken there.

Or is that unlikely? Would in a healthy environment that checkpoint probably pop back to normal, too?
Or am I missing something altogether?
 

leokitten

Senior Member
Messages
1,541
Location
U.S.
One thing irritates me: This whole positive feedback loop can only exist, because somewhere a checkpoint doesn't work, and keeps on not working. So, why then, when we interrupt the feedback loop, would this checkpoint suddenly work again afterwards? Because otherwise the next viral infection, the next inducing of IFN-alpha would bring us right back into the feedback loop, wouldn't it? That would mean, one had to fix that checkpoint, be it by killing off viruses or whatever else is broken there.

Or is that unlikely? Would in a healthy environment that checkpoint probably pop back to normal, too?
Or am I missing something altogether?

This is right on point and another way of saying what I wrote in my question 1) above
 

leokitten

Senior Member
Messages
1,541
Location
U.S.
So what caused our innate immune system checkpoints to not work properly in the first place… is it genetics, environment (eg chronic stress weakening the immune system or dysfunctional over time, or life stressors at the time of triggering infection), inability of our immune system to be able to promptly clear certain infections resulting in extended time in activated state thereby increasing the risk that it gets stuck on, inability of our immune system to be able to keep ubiquitous chronic infections in a dormant state thereby triggering constant antigen exposure?

Brings to mind the phenomenon that most people with LC (and ME as well) had a so called “mild” infection that didn’t require hospitalization. Why does a “mild” infection paradoxically increase the chances of getting this immunometabolic dysfunction?
 
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BrightCandle

Senior Member
Messages
1,133
Or is that unlikely? Would in a healthy environment that checkpoint probably pop back to normal, too?
Or am I missing something altogether?

I don't think its certain it would only that it might. If we took damaged DNA as an example then only certain tissue in the body is damaged and sustaining the problem and so long as that particular tissue didnt feel threatened we wouldn't get stuck into ME/CFS again.

But even if we got ME/CFS again after every cold if it really was just 3 days on some blocking drug once it passed and we were back to normal I'll take it, that is a treatment as close to a cure as I have ever heard of. We would all just be keeping a dose in our drawers incase we got knocked back again and we would wait for the virus to clear and then isolate and dose and be back to normal. It means a cold would be more 2 weeks than 1 for us but as consequences go I'll take it!
 
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Oliver3

Senior Member
Messages
839
So what caused our innate immune system checkpoints to not work properly in the first place… is it genetics, environment (eg chronic stress weakening the immune system or dysfunctional over time, or life stressors at the time of triggering infection), inability of our immune system to be able to promptly clear certain infections resulting in extended time in activated state thereby increasing the risk that it gets stuck on, inability of our immune system to be able to keep ubiquitous chronic infections in a dormant state thereby triggering constant antigen exposure?

Brings to mind the phenomenon that most people with LC (and ME as well) had a so called “mild” infection that didn’t require hospitalization. Why does a “mild” infection paradoxically increase the chances of getting this immunometabolic dysfunction?
Strength and tissue type
 

Alvin2

The good news is patients don't die the bad news..
Messages
2,939
Finally watched the new vid, and did some research on possible treatments (the jak stat mentioned), found these links:
https://www.lifeextension.com/magazine/2012/10/powerful-protection-against-cellular-aging
https://www.lifeextension.com/magazine/2013/8/pqq-vitamin-d-skin-aging-and-coffee
I have tried PQQ, 20mg once daily, no effect but might need higher dose?

Astaxanthin and JAK
https://www.lifeextension.com/magaz...-nails-plant-protein-rhodiola-and-astaxanthin
https://www.lifeextension.com/magazine/2017/12/update-astaxanthin

Gonna try this when i can get some. No idea of the dose is right
https://www.healthyplanetcanada.com/natural-factors-astaxanthin-plus-4mg-60-softgels.html

https://en.wikipedia.org/wiki/Janus_kinase_inhibitor
Chemotherapy drugs, not easy to get or safe to DIY