Professor Ron Davis's response to Naviaux study, including Q and A with Dr Naviaux

[alex3619]

The questions being asked are good questions, but some of them are so far in advance of current research that answers would be highly speculative at this point in time. This type of research will probably be fruitful for years, and most of the questions might be answerable in five to ten years, but I doubt most will be answered this year, or even next year.

Having said that I am only too happy to hear speculations, provided they are clearly labelled as hypothesis, speculation, etc.

 

[Kati]

The questions being asked are good questions, but some of them are so far in advance of current research that answers would be highly speculative at this point in time. This type of research will probably be fruitful for years, and most of the questions might be answerable in five to ten years, but I doubt most will be answered this year, or even next year.

Having said that I am only to happy to hear speculations, provided they are clearly labelled as hypothesis, speculation, etc.

Agreed. I shared the PNAS abstract with my family doctor today and the first thing she said is 'well you know, first this study has to be replicated' (which of course I knew). At this point I simply wanted her to understand it wasn't in my head . I may actually be stuck in that convincing behavior for a while more. The doctors here have been brainwashed. We have a lot of 'cleaning' to do.

 

[alex3619]

We have a lot of 'cleaning' to do.

Deprogramming?

 

[Kati]

Deprogramming?

Yes, erase the hard drives... Start with a new kind of medicine.

 

[alex3619]

Yes, erase the hard drives... Start with a new kind of medicine.

The term is also used in changing the views of those brainwashed by cults, but I think the computing analogy is where it originates.

 

[alex3619]

has to be replicated

There are three studies under way or completed, at least, plus the follow up study from the first one. Replication is mostly done. Further testing is needed to determine things like specificity and sensitivity, but we will get there.

 

[Daisymay]

Deprogramming?

Yes, a course (maybe it will take several courses...) of CBT to change their wrong illness beliefs!

 

[Nielk]

@Ben Howell - thank you for all your help in being an intermediary and aiding in clarifications.

I would want to ask Dr. Davis and the authors of this study how they would explain the evidence that ME patients are suffering from chronic neuroinflammation. This has been shown in studies of brain scans and spinal fluid.

This was the finding of Dr. Ramsay as well and that is why he called the disease myalgic encephalomyelitis.

Many ME patients have other evidence of ongoing inflammation in the body. ME specialists have treated these patients with antivirals and Ampligen - bringing some relief for many of their patients.

These patients suffer from the effects of an ongoing pathogen - whether it is embedded in the brain, appears in the blood or tissue of the patient.

These patients have ongoing symptoms of inflammation as well. They are not just exhausted - they suffer from sore throats, chills, acute headaches, enlarged lymph nodes and much more.

These patients do not match the picture of the one presented by a dauer state - where there was a (or more than one) trigger and the body, in a defensive mode, is going into a depressed mode and then gets stuck there.

The authors state that if this defensive state continues beyond six months - it can be called CFS. Mayne so but, it does not in my view explain myalgic encephalomyelitis.

In addition, there is confusion about the criteria used for all patient cohorts for the study. The authors list Fukuda, IOM and CCC. It would be good to clarify whether all cohorts fulfilled all these criteria. It is confusing - because the IOM are diagnostic criteria - not research. The Fukuda criteria do not define ME since the hallmark symptom of PEM is just optional.

 

[Ben H]

@Ben Howell if you don't mind I have a question -

At iime conference 2016 Maureen Hanson presented a slide from a metabolite study which indicated 100% success at identifiing ME/CFS patients from controls. Do we have any info on whether Dr. Hansons results correlate to Naviaux's results ?
I appreciate you may not know the details of Hanson's study, no problem if not.Tks.

Hi @BurnA. I do not know the details of this as I did not catch the event unfortunately. @Snowdrop kindly provided a link which I've read, but doesn't have all the details regarding metabolomics. Sorry!

@Ben Howell and anyone else.... I am curious how some of us have ME and an inflammatory disease?

According to my understanding of Naviaux's research they show up very differently.

"we found that the direction of CFS abnormalities was opposite to metabolic syndrome (37) and opposite to the metabolic response to infection, inflammation, or environmental stress that has been called the CDR".

How is it possible then that I see lots of ME patients discussing inflammatory diseases that they have as well as their ME? (I am talking about chronic inflammatory conditions not acute ones). Unless I have misunderstood (brainfog...) and the inflammation referred to in the research is of an acute nature?

Great question, and one for Dr Naviaux.

@BurnA
If you haven't seen it already have a look here for answer to Q: http://forums.phoenixrising.me/index.php?threads/maureen-hansons-presentation-at-solve-cfs.46580/

Edit: what dancer said. Just saw her response.

Thanks for posting @Snowdrop. I'd like to see the full details.

@Ben Howell

As you are kindly collecting questions, I have one too (though I doubt there will be an answer, but I'm interested even if Drs Naviaux & Davis have a hunch about this):

If more evidence is gathered supporting this notion of ME/CFS being a dauer-like state, I wonder about treatment. Many people try treatments, which might have some benefit for a while before losing their efficacy, suggesting a homeostatic quality about the state. Is treatment likely to be a matter of bringing us out of the state safely and then we're done (which, granted, may take time), or is it likely that treatment will require ongoing maintenance to keep us that way?

Another great question. Noted for Dr Naviaux. As Alex has said we may not have an answer for this yet, having no clinical trial for treatments being run. This is the first-gigantic-step towards this however.

@Ben Howell Here are my questions, sorry if they are redundant.

1) Did the 600 metabolites include a snapshot of the brain's metabolic state vs the body's metabolic state? If not would it be possible to study that? I.e. a metabolic profile of the cerebral spinal fluid vs the blood.

2) Can the hypometabolic state be taken to directly cause the symptoms of fatigue & PEM? Or is it further up the chain.

3) Will they profile the metabolic state of Fibromyalgia?

Hi @dreampop

1.) The metabolomics run in Naviaux's study was using blood, not tissue. So you may expect some differences between the two. However, the metabolic state of the body would affect brain function and is representative of overall metabolism.

2.) One for Dr Naviaux, I don't want to speculate.

3.) I believe this was mentioned, as one of the diseases to be cross referenced with regards to metabolomics. Will try to find out for you, but @Rose49 may be able to get an answer. OMF need funding for this study and future studies.

I'd like to hear Naviaux's take on this as well from his perspective; what could be some hypothetical explanations of PEM, specifically the immune activation symptoms, under this model?

I'd also be curious to hear thoughts on how our selective neuropathies could be explained as well.

Noted, thanks @halcyon.

@Ben Howell - thank you for all your help in being an intermediary and aiding in clarifications.

I would want to ask Dr. Davis and the authors of this study how they would explain the evidence that ME patients are suffering from chronic neuroinflammation. This has been shown in studies of brain scans and spinal fluid.

This was the finding of Dr. Ramsay as well and that is why he called the disease myalgic encephalomyelitis.

Many ME patients have other evidence of ongoing inflammation in the body. ME specialists have treated these patients with antivirals and Ampligen - bringing some relief for many of their patients.

These patients suffer from the effects of an ongoing pathogen - whether it is embedded in the brain, appears in the blood or tissue of the patient.

These patients have ongoing symptoms of inflammation as well. They are not just exhausted - they suffer from sore throats, chills, acute headaches, enlarged lymph nodes and much more.

These patients do not match the picture of the one presented by a dauer state - where there was a (or more than one) trigger and the body, in a defensive mode, is going into a depressed mode and then gets stuck there.

The authors state that if this defensive state continues beyond six months - it can be called CFS. Mayne so but, it does not in my view explain myalgic encephalomyelitis.

In addition, there is confusion about the criteria used for all patient cohorts for the study. The authors list Fukuda, IOM and CCC. It would be good to clarify whether all cohorts fulfilled all these criteria. It is confusing - because the IOM are diagnostic criteria - not research. The Fukuda criteria do not define ME since the hallmark symptom of PEM is just optional.

Hi @Nielk,

I've sent Dr Naviaux a list of questions which include systemic inflammation and how that may fit with the findings.

I think it pertinent to remember that its the FIRST study ever conducted testing metabolomics in the blood on a cohort of patients with ME/CFS, The findings are extremely promising, but preliminary. It will be very interesting to see the results of the Severely Ill BIG DATA study which is measuring a huge amount of markers, aswell as metabolomics and maybe able to answer your question better. Linky: http://www.openmedicinefoundation.org/phase-i-list-of-tests/

You mention that:

''These patients have ongoing symptoms of inflammation as well. They are not just exhausted - they suffer from sore throats, chills, acute headaches, enlarged lymph nodes and much more.

These patients do not match the picture of the one presented by a dauer state - where there was a (or more than one) trigger and the body, in a defensive mode, is going into a depressed mode and then gets stuck there.''

I wrote a reply to this, but on reflection feel it best for Dr Naviaux to answer. I am not a scientist and this interaction is extremely complex. In my view I do not see this as an not fitting with the findings, and believe it can be explained by metabolism and the metabolomics, but would like Dr Naviaux to reply.

Good questions, and important ones.

When Dr Naviaux has a chance to reply, I will (or Janet) will update you and the thread.


B

 

[Chris]

Another question--given that the red and Near InfraRed light used in LLLT/Photobiomodulation has as its first effect the raising of ATP production within the mitos by being absorbed by cytochrome oxidase (this is pretty well established) while then going on to increase ROS signaling, is it likely to be helpful, or to be used with the greatest discretion, and delivered very slowly, with breaks, as my experience suggests? Any comments?

 

[Biarritz13]

@Ben Howell

1/Have Ron and Naviaux speculate about why there is a hypo-perfusion in some regions of the brain?

2/ Is this symptom more a cause or a collateral damage?

3/ What HBOT can do on a metabolite basis?

 

[Gingergrrl]

Many ME patients have other evidence of ongoing inflammation in the body. ME specialists have treated these patients with antivirals and Ampligen - bringing some relief for many of their patients.

These patients suffer from the effects of an ongoing pathogen - whether it is embedded in the brain, appears in the blood or tissue of the patient.

These patients have ongoing symptoms of inflammation as well. They are not just exhausted - they suffer from sore throats, chills, acute headaches, enlarged lymph nodes and much more.

@Ben Howell I have a question for the researchers re: how they conceptualize the patients who are the opposite of this description- who have not benefitted from anti-virals and who have never had sore throat, chills, acute headaches, fevers, or enlarged lymph nodes at any point during their illness vs. having an acute virus (plus other triggers) and then at a later point developing an ME/CFS type illness that presents with dysautonomia, muscle weakness, and an overall autoimmune presentation (i.e. skewed to the Th2 side with acute allergic reactions, autoantibodies, etc)?

Would they view the latter group as a different illness or just a sub-set within the larger illness? I have no agenda or theory and am asking b/c this issue confuses me greatly.

 

[bertiedog]

These patients have ongoing symptoms of inflammation as well. They are not just exhausted - they suffer from sore throats, chills, acute headaches, enlarged lymph nodes and much more.

For sure I suffer with all these quite regularly but on the other hand I can have good energy as long as I have lots of rests in between because I run out of energy after 30 minutes maximum. I am positive there has to be subsets in this illness.

Pam

 

[natasa778]

Geoffrey Burnstock had a lot to say on that at 2011 InvestinME conference. He was focusing his talk on 2-3 (subsets of) purinergic receptors that he thought would probably be of most relevance and the ones to target in ME. I made detailed notes of the talk but don't know if I still have them saved them and where

Ok, I've actually found a couple of scribbles I made during the talk.... Copying here on the off chance that some of it could be of some use to someone

ATP== importance as a signalling molecule, not only the usual energy role... (inflammation)

P2X4 receptors ---> immune cells

P2X4 antagonists? (paroxetine!) also P2X7 receptor blocking helps neuropatic pain​

Few papers on paroxetine's effects on purinergic receptors ... also here on neuropathic pain relief via P2X7 purinergic blockade


Geoffrey Burnstock (2002) Potential therapeutic targets in the rapidly expanding field of purinergic signalling


Edited to add:

for anyone interested in exploring further, this paper gives a good overview. It is not free access, but apparently there is that thingy called sci-hub.cc ...

Membrane compartments and purinergic signalling: P2X receptors in neurodegenerative and neuroinflammatory events

In this minireview, we highlight the contribution of the subclass of ionotropic P2X receptors to several diseases of the human nervous system, such as neurodegenerative disorders and immune-mediated neuroinflammatory dysfunctions including ischaemia, Parkinson’s, Alzheimer’s and Huntington’s diseases, amyotrophic lateral sclerosis and multiple sclerosis. The role of P2X receptors as novel and effective targets for the genetic/pharmacological manipulation of purinergic mechanisms in several neuropathological conditions is now well established. Nevertheless, any successful therapeutic intervention against these diseases cannot be restricted to P2X receptors, but should take into consideration the whole and multipart ATP signalling machinery.

 

[Groggy Doggy]

Hi @Ben Howell

Here are my questions:

What medications & vaccines did the study patients take one year prior to being ill and since they have been ill.

What tests were run to rule out other illnesses like:
hypopituitary, Panhypopituitary, Hypoparathyroidism, lipodystrophy (or other leptin disorders)

Is there any history of head trauma.

Thank you very much!!

Muchas gracias!
Merci beaucoup!
Grazie mille!
Veel dank!
Vielen Dank!
Tack så mycket

 

[Gingergrrl]

Muchas gracias!
Merci beaucoup!
Grazie mille!
Veel dank!
Vielen Dank!
Tack så mycket

Just being silly but am adding "Thank you" in two more languages for @Ben Howell and apologize if the spellings in English are a bit off:

Toda Rabah (Hebrew)
Kamsa Hamnida (Korean)

 

[paolo]

@Ben Howell

As the dauer-like hypometabolism has a pattern opposite to the one seen in response to acute infections, is it possible that the efficacy of Ampligen in a subset of PWME may be due to its ability to artificially induce the immune response of an acute viral infection?

 

[Daisymay]

@Ben Howell

As the dauer-like hypometabolism has a pattern opposite to the one seen in response to acute infections, is it possible that the efficacy of Ampligen in a subset of PWME may be due to its ability to artificially induce the immune response of an acute viral infection?

Wow yes, how intereting to see people's metabolomic results before during and after treatment with ampligen, ritux etc etc to see how these things may be working at this level to help some people and which people.

 

[Gingergrrl]

Wow yes, how intereting to see people's metabolomic results before during and after treatment with ampligen, ritux etc etc to see how these things may be working at this level to help some people and which people.

I did the metabolon test in May 2015 (not for a study and it was not run but blood was bio-banked) and it was at the very worst point of my illness. If it is humanly possible (still not sure) I'd like to run the test with that blood and then do it again in a year (or whatever timeframe?) after I complete a full course of IVIG and later RTX and see how they compare and also what symptom improvement I have. It won't be part of a study but would still be interesting!

 

[viggster]

In addition, there is confusion about the criteria used for all patient cohorts for the study. The authors list Fukuda, IOM and CCC. It would be good to clarify whether all cohorts fulfilled all these criteria.

From page 7 of the paper: "All CFS patients met the 2015 IOM (4), Canadian (8), and Fukuda (9) diagnostic criteria for CFS."