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

[KME]

Hi @A.B.

This is where the genetic part of the studies are likely to come into play.

I am in total agreement with Ron that strongest signals would logically be expected to be found in the most severely ill. What is the basis of your argument for the strongest signal (as opposed to just a signal) being in families? If they are all mild, that may not be so. The SD's may not be far from the norm unlike the recent Naviaux study, and Whitney for example.

I agree that families diagnosed with ME/CFS would be a very important study. Especially from a genetic perspective. I would love to see it run. It all comes down to funding, this is all still publically funded so while I am sure Ron would like to do a study on families with ME/CFS, there is only a limited pot to go round.

I will note this down as I think its a really good, interesting question and if Ron has the time, I'd love to see his answer.

Thanks,

B

And Dr Avi Nath of the NIH study thinks it's most important to look at those closest to the trigger, which is why that study is looking at post-infectious patients in the first few years (5, right?) He has described it as needing to know where the epicenter of the earthquake is, rather than where the devastation is greatest.

I think there's a rationale for all, and all should be studied. I'd love to see a family study - I think it's important, particularly given the rituximab findings.

I think we could get really key information from each of these extreme groups - families, severe and early. A potential difficulty with looking at early patients is that you will have more of a mix of those who are going to improve and those who are not going to improve, which could muddy the data. So there's a rationale for focusing on long duration patients too! We won't know where the biomarkers are strongest until we look. In many autoimmune diseases, some people can be symptomatic for many years before any of the biomarkers for their autoimmune disease show up, if they show up...

 

[Ben H]

I hope @A.B. won't mind me jumping in here. I had to read that first quote above a couple of times to get the distinction that I think A.B. is making.

The signal of the illness will be strongest in those that are severely ill - as in the impact it is having on the body.

But the signal of the cause of the illness will be strongest in multiple cases in a family. These signals of causality might be genetic or related to onset (triggering factors). There may even be clues from the metabolites as the outcomes may be clearer with less genetic diversity and especially if there is a gradient of illness severity within the family.

Hi @Hutan

I get what you are saying. Personally I'm not so sure about the 'signal of the cause of the illness' being strongest in multiple family cases. We have no evidence for that yet. Genetics will surely contribute, but I think under a 'perfect storm' scenario. That is, genetics may predispose you to ME/CFS, but not cause it unless other factors are present.

There will surely be families and individuals with genes that are found to impact ME/CFS, that do not get the illness. And probably people that don't have the genes that DO get ME/CFS.

But, I may be totally wrong-we need to wait and see, and hopefully get enough funding where a study like this is possible.

I will forward to Janet/Ron.


B

 

[A.B.]

But the signal of the cause of the illness will be strongest in multiple cases in a family. These signals of causality might be genetic or related to onset (triggering factors). There may even be clues from the metabolites as the outcomes may be clearer with less genetic diversity and possibly a gradient of illness severity.

Thanks for jumping in. I'm not always good at expressing myself. The red part is particularly important. My impression is that the symptoms vary somewhat even between family members, yet it is likely that all of them got ill for the same reason. So the answer probably lies in what they have or had in common with each other. Studying these illness clusters is a way to simplify the problem of finding out what causes the illness, and I think it will reduce costs since you won't need as many patients to reach statistical significance on the things they have in common.

I'm no researcher but the above seems to make intuitive sense to me.

 

[Ben H]

Thanks for jumping in. I'm not always good at expressing myself. The red part is particularly important. My impression is that the symptoms vary somewhat even between family members, yet it is likely that all of them got ill for the same reason. So the answer probably lies in what they have or had in common with each other. Studying these illness clusters is a way to simplify the problem of finding out what causes the illness, and I think it will reduce costs since you won't need as many patients to reach statistical significance on the things they have in common.

I'm no researcher but the above seems to make intuitive sense to me.

I agree- @Hutan 's bold there does make sense, intuitively. I think it could be a really good potential study. Funding is the main issue!


B

 

[Gingergrrl]

n many autoimmune diseases, some people can be symptomatic for many years before any of the biomarkers for their autoimmune disease show up, if they show up...

I don't think I realized that and it is very helpful to learn, thank you!

 

[actup]

I have family chock full of pwcfs-1st and 2nd degree relatives. No doctor bias as diagnoses were made over a 25 yr period by various mds in Dallas, Portland and Seattle ( 2,000 driving miles from Seattle to Dallas and almost 300 between Portland and Seattle).

The only environmental commonality I can find so far is having lived for 10 yrs or more in the Pacific NW (less sun due to heavy cloud cover) with low vit d levels. Agree w @A.B. and @Hutan that family clusters are low hanging fruit -I like that sentence.

 

[alicec]

I hope this thread can take a lighter perspective now

Yes, but I am still gobsmacked by the attitude of @boohealth - s/he has nothing to gain from talking to Ron Davis but Ron may get some valuable insight that will help his son !!!!

 

[Bob]

Yes, but I am still gobsmacked by the attitude of @boohealth - he has nothing to gain from talking to Ron Davis but Ron may get some valuable insight that will help his son !!!!

Luckily 99.9% of our community know that we have everything to gain from the soaring scientific insights and hard work that Ron brings to our illness.

 

[valentinelynx]

Yes, but I am still gobsmacked by the attitude of @boohealth - he has nothing to gain from talking to Ron Davis but Ron may get some valuable insight that will help his son !!!!

Please, folks, I think @boohealth is being misunderstood... lord knows, I've stuck my foot in it a few times online. It's just too easy to say something that's not quite the right tone. I think he just meant to say that he was trying to offer something rather than take something? Plus, I don't think he knew coming into it just how much esteem this group has for Dr Davis, and now he's really in the doghouse. It's not easy sometimes to express yourself coherently when you have this illness. Just suggesting we offer a little slack...

 

[Gingergrrl]

Please, folks, I think @boohealth is being misunderstood...

It's not easy sometimes to express yourself coherently when you have this illness.

I respectfully disagree and don't think boohealth is being misunderstood because she (he?) has expressed the same sentiment in about 5-6 separate posts like below which are verbatim:

As to the rest, @Gingergrrl suggested I read this entire thread (which expands voluminously daily) and consider myself lucky and act now. I don't have time to read this whole thread. Nor would it necessarily be useful.

If I were to be offered a free Skype consult with Dr. Davis, I would absolutely consider myself lucky and I would act now. If I were told my consult was tomorrow at 2:00 AM, I would stay up all night preparing and would be thanking God for the opportunity presented to me. I would also read this thread in it's entirety and would find it very useful as part of my preparation.

I did criticize him.

Boohealth admits to criticizing him and it was not b/c of not being able to communicate coherently b/c of the illness per her own words. She disagrees with him (which is certainly okay!) but we can express disagreement and still be polite and not insult someone's personal or professional character.

Of course a scientist of his caliber can cope with these type of comments and is likely un-phased by them but the risk is that he or Dr. Naviaux could decide, "Why bother answering lists and lists of questions complied by Ben when the members of PR are unappreciative." I don't want to run that risk plus I just find it rude.

And I agree with Bob that 99.9% of us grasp the enormity that we have direct access to speak with such renowned scientists. I hope the scientists know this as well and that they know that we do not take this opportunity for granted.

 

[Sushi]

The thread title is:

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

Please keep this thread on topic.

 

[mermaid]

@Ben Howell This morning I had a lightbulb moment with regard to the study, but I am no scientist so please feel free to shoot it down!

I am diagnosed with both hypothyroidism and ME/CFS, the hypothyroid condition long before the ME/CFS, so it's properly recognised with high TSH and all that....I took T4 only for 17 years before I began to explore other options due to lack of function (by this time I also had the ME/CFS label).

Having read a lot around the subject I understood that there were some on T4 only who believed that their T4 only medication was not being converted in the body to T3 very efficiently, thus meaning that their hypothyroid condition was not well managed, and they still felt ill in many ways. Blood tests may show all is OK with the TSH, but they are unable to check the tissues which may show a different story.

NOW.... if this new research indicates that we with ME/CFS are in a state of hypometabolism, would this not impact on the way someone who was on T4 only would convert to T3 in the body? Depending on how ill we were at any one time, then everything would slow down?

It's of particular interest to me, at the moment, as the 'powers that be' (ie the local CCG) have just decided that I may no longer have T3 due 1. to the cost and 2. backed up by their research which says I believe that it's detrimental (I need to check the research on it recently which I think says this). I am just trying to fight this but can see that I am up against a brick wall if they don't take this metabolic effect in the body into account.

What do you or anyone else think of my theory? (a non scientist as I said).

 

[dreampop]

@Ben Howell

Sorry for so many questions, but I wanted to emphasize that I'd really appreciate the question of brain/cerebral spinal fluid metabolic profile being asked to Davis or Naviaux. In a recent blog @Cort brought up the findings of abnormal metabolites in Major Depressive Disorder and the discovery of an abnormally low metabolite in some patients. I think there's many reasons to believe that a unique biomarker in the CSF may be even more likely than in the body. So many of the symptoms unique to CFS are in some way centrally governed and some of the findings from all sects of medicine have consistently pointed to the brain stem and prefrontal cortex as behaving abnormally. I really hope he would consider the possibility (obviously I know, if the money allows).

It seems even more important considering a hypo-metabolic state would pose a unique challenge to the brain as a high energy consumer with less flexible mitochondrial ability - and with poor perfusion. I'm not confident that the metabolic profile of the body would necessarily tell us whats going on in the brain.

 

[Janet Dafoe]

@Valentijn , you left out the first lines of my post To leap now without preparing would waste his time.

As to the rest, @Gingergrrl suggested I read this entire thread (which expands voluminously daily) and consider myself lucky and act now. I don't have time to read this whole thread. Nor would it necessarily be useful.

I did criticize him. I'll have to take the blows for that on PR, some of which I've likely missed because people aren't tagging me. But it was very generous of Janet to answer as she did, and I'm happy about that.

I think everyone can calm down about this. @boohealth has said he would prepare his ideas to tell Ron about. Ron is always interested in hearing new ideas. I am confident that @boohealth will be respectful. Ron is just a regular guy and is able to listen. He will probably respond, too. It should be interesting. I will be there too. If it gets too weird then we can just stop. But I highly doubt that will happen! I'm looking forward to it. Ron just smiled when I told him what was said. He's not particularly fragile. And he's not going to get scared off, either. He's dedicated. He's perfectly able to realize that there are a lot of people who benefit from hearing his comments. Let's get off of this and move on to just trying to figure out ME/CFS, ok? We should all just unite against the people who aren't funding us! And advocate with everyone we know for donations and funding! Go Team!

 

[Janet Dafoe]

@Ben Howell

Sorry for so many questions, but I wanted to emphasize that I'd really appreciate the question of brain/cerebral spinal fluid metabolic profile being asked to Davis or Naviaux. In a recent blog @Cort brought up the findings of abnormal metabolites in Major Depressive Disorder and the discovery of an abnormally low metabolite in some patients. I think there's many reasons to believe that a unique biomarker in the CSF may be even more likely than in the body. So many of the symptoms unique to CFS are in some way centrally governed and some of the findings from all sects of medicine have consistently pointed to the brain stem and prefrontal cortex as behaving abnormally. I really hope he would consider the possibility (obviously I know, if the money allows).

It seems even more important considering a hypo-metabolic state would pose a unique challenge to the brain as a high energy consumer with less flexible mitochondrial ability - and with poor perfusion. I'm not confident that the metabolic profile of the body would necessarily tell us whats going on in the brain.

I know Ron would love to analyze spinal fluid. However, he is extremely dedicated to finding a biomarker that is accurate and non-invasive! And inexpensive. Same with Naviaux. In the Severely Ill Big Data Study he would not even ask anyone for spinal fluid. It would be too hard on the patients. He's pretty confident that we can get there without such invasive procedures. Using the stress test is another example. It's too hard on people. We do not want to make people worse in the process of diagnosing them if that can be avoided! I'm not sure what the question was - I'm having trouble getting through all these posts, but hopefully this answers at least part of the question!

 

[Riley]

I know Ron would love to analyze spinal fluid.

@Rose49 I believe that Dr. Daniel Peterson in Nevada has a significant collection of spinal fluid samples taken from patients over the years. Maybe Ron could use them if he has an idea for a study.

 

[Nielk]

@Rose49 and @Ben Howell - We are so grateful to both of you for your time and effort in answering the many questions here on this thread.

I had previously asked about how Dr. Davis would explain the fact that ME patients have ongoing symptoms of chronic inflammation in the body. This has been backed up with evidence of ongoing neuroinflammation and elevated viral titers. Many ME experts have treated these patients with some success with antivirals and Ampligen. (see this post http://forums.phoenixrising.me/inde...d-a-with-dr-naviaux.46520/page-15#post-758657)

In other words, there is evidence of an ongoing pathogen harming the patients. It is not merely tired patients who are stuck in a lowered metabolic state because of a past trigger (which now is gone).

In addition, I was surprised to see that the next step suggested was a comparison with depression and PTSD patients. Why were these groups selected? Why not compare with MS and RA patients?

 

[trishrhymes]

Neilk says: 'In addition, I was surprised to see that the next step suggested was a comparison with depression and PTSD patients. Why were these groups selected? Why not compare with MS and RA patients?'

Sorry, forgotten how to insert quote.

As I understand it, Naviaux is not a specifically ME researcher. He can only research other conditions if he gets funding to do so, and I assume he has funding in place to investigate depression and PTSD.

I can't see a problem with comparing the findings on ME with these conditions. A lot can be learned from seeing whether there are distinguishable differences in metabolites between ME and any other condition.

 

[duncan]

A lot can be learned from seeing whether there are distinguishable differences in metabolites between ME and any other condition.

No one would dispute this. But it is the category of conditions mentioned that is worrisome. After all, our disease is not diagnosed or perceived in a vacuum. We fight against the onus of a "mental" label daily - or at least a label that usually goes hand in hand with talk therapies and psychogenics.. There are ramifications to this association, at least potentially. I cannot see how this comparison with depression and PTSD will help mitigate that bias, and it is puzzling out of all the diseases and conditions, these two would be selected. How about MS or brain cancer? Or Parkinsons and RA? Any help in explaining the choices would be appreciated.

 

[Tuha]

@Ben Howell

will there be soon a release about their future research plans? This could be interesting what they plan in the near future. This could be also good for their marketing.