Robert Naviaux' Lab - News - from 2019 onwards

[Snow Leopard]

Thanks @forestglip and @bicentennial. I forget, do we have any evidence of higher levels of extracellular ATP in people with ME/CFS?

There is no generalised increase in extracellular ATP, but there could be in specific tissues.

Sympathetic nerves secrete eATP which can activate purinergic receptors.
https://www.sciencedirect.com/science/article/abs/pii/S1054358908607103

I don't believe the issue is the "cell danger response" as described by Naviaux, but stimulating those receptors can have specific consequences including increased fatigue sensation (or pain in the case of Fibromyalgia).

 

[Jonathan Edwards]

I've completely lost track of this whole cell danger line of inquiry. How is it going?

I think the idea of a persistent 'danger' response is quite plausible.
However, all Naviaux seems to have produced is a mish-mash of speculation that provides no actual explanation for why anything persists.
And there are no data whatever to support anything.

It is hard to take seriously an approach that is so uncritical about anecdotes about spines and suchlike.

 

[Mij]

It sounded so contrived I couldn't make myself take it seriously. And anyway, as soon as CCI comes into a conversation about ME/CFS I'm away on my toes.

Indeed. Stomp it like it's on fire!

 

[Amw66]

Thanks @forestglip and @bicentennial. I forget, do we have any evidence of higher levels of extracellular ATP in people with ME/CFS?

Is it ever tested for ?
It's hard enough getting anything other than a standard FBC if you have ME/ CFS

Early on we did the Myhill mitochondrial test which has not been replicated successfully .
My aunt did it too. I would have to find the test results for full details , but I remember that There was interesting info . It did look at ATP.

My daughter had not been ill for as long as my aunt -she had a paediatric referral but we had not been yet .
My aunt was bedbound by then

My daughter was chucking out ATP significantly - so signalling .
SOD was off ( think it was MnSOD, but not sure)
B3 was off
Magnesium low

My aunt's data seemed to suggest something wrong with translocator function . It has been suggested that some chemicals can do this , as she was a hairdresser briefly and then a florist - both professions being exposed to many chemicals .
ATP low
Magnesium low
SOD off - but a different SOD from my daughter
Probably other differences too

Interestingly the " score" achieved on this test by combining the individual results was uncannily accurate relative to Bell score .

 

[Hutan]

Is it ever tested for ?
It's hard enough getting anything other than a standard FBC if you have ME/ CFS

@Snow Leopard's noted that any release of extracellular ATP is probably acting on tissues super locally, so could be very hard to identify in blood tests.

 

[Murph]

I remember a long thread about purinergic signalling; what I learned from that is that eATP

1. breaks down fast
2. operates on the cell it came out of (autocrine signalling) and a few nearby cells (paracrine signalling).
3. exists in a thin, tiny "halo" around the cell

So you can't expect to measure it in blood.

I do find eATP to be a plausible issue, especially as a link between vascular and immune issues. Erythrocytes emit ATP when they get squished and squashed, via a mechanical process. (e.g. the blood vessel they are trying to move through hasn't widened enough, so they get jostled, callled shear stress, and then emit ATP). This is one of the signals we use to dilate blood vessels. But if the dilation doesn't happen sufficiently (perhaps due to some problem in endothelial cells or nitric oxide response), I wonder if lots of eATP could be produced.

That could perhaps trigger those endothelial cells to call in a bigger immune/homeostatic response, or, alternatively running the erythrocytes out of ATP could cause problems.

If it were the former issue (endothelial cells can't use ATP to dilate vessels but can sense excess ATP and use that to trigger a broader response) then suramin may be useful. It's a plausible hypothesis but purely speculative.

 

[Kitty]

Trouble is, the theories don't seem to get tested. It appears to be more about weaving stories than doing science.

If an idea's speculative, linking it to other speculative ideas doesn't add any weight to it. It might make it sound more interesting, but you're still only building a ladder to the moon. There comes a point where you need to stand on it to see if it stays up.