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

[Sidereal]

Superb.

 

[paolo]

Whoops, Ben, not true. Whitney has had his metabolomics done at Metabolon, and also by Naviaux several times.

@Rose49

At this point would you suggest to patients to send their blood in order to have the metabolic test done? Or is it better to wait for more definitive results and for an improved test?

Thanks so much for all your efforts!

 

[Janet Dafoe]

@Rose49

At this point would you suggest to patients to send their blood in order to have the metabolic test done? Or is it better to wait for more definitive results and for an improved test?

Thanks so much for all your efforts!

Laurel Crosby, in Ron's lab, is working on a way for patients to do this at greatly reduced cost at Metabolon. She will announce how to do it shortly.

 

[paolo]

Laurel Crosby, in Ron's lab, is working on a way for patients to do this at greatly reduced cost at Metabolon. She will announce how to do it shortly.

Thanks so much! To you, Ron Davis, and Laurel Crosby.

 

[Janet Dafoe]

Thanks @Ben Howell and I am also very curious about this and would appreciate the info! It sounds like my sample from May 2015 that was bio banked but not tested probably is no longer valid for the metabolites after all?

Am curious to learn what Dr. Davis and Dr. Naviaux feel is the cut off period and I don't want to run the sample if it wouldn't be valid and would rather do a new test through OMI once it becomes available.

I'm not aware that OMI is doing this. I don't think so. It will be available soon through Laurel Crosby at the CFSResearch Center at Stanford.

 

[hixxy]

Laurel Crosby, in Ron's lab, is working on a way for patients to do this at greatly reduced cost at Metabolon. She will announce how to do it shortly.

Can many doctors actually make use of this test clinically? Can it currently be used for anything other than curiosity and checking results against Dr Naviaux's research?

 

[Janet Dafoe]

Can many doctors actually make use of this test clinically? Can it currently be used for anything other than curiosity and checking results against Dr Naviaux's research?

I'm going to ask Ron and Dr. Naviaux to answer this. I know that in the absence of NIH funding, it is hard to get all the data. This is a way, similar to what Nancy Klimas is doing with 23 and Me, for patients to get info about their own metabolomics and DNA and really help the research by allowing the scientists to have it. They are working as fast as they can to figure out the treatment. And yes, disseminating that to doctors all over the country is going to be a big job. But with this amazing patient community, you guys can help. Once we know, you can help get it out there. And websites or something will be set up to help docs figure out what to do. For now, it will be amazing for you all to see what is going on in your own bodies, which up until now many of you have been told that nothing is wrong. When we first saw Whitney's metabolite data it was the most affirming thing EVER. Finally we could see that something was indeed terribly wrong in lab tests! It was a jaw dropping moment. Of course, we knew something was wrong, but most of the tests had come out pretty normal up till then. Anyway, it will be a good thing for people to be able to get their own data, and for their doctors to see. Figuring out how to treat is being workied on as fast as possible. Ron might be able to say more.

 

[trishrhymes]

And? How did the results compare to Naviauxs overall findings?

Surely that's his private medical data, not something we should ask him or his family to share.

 

[Janet Dafoe]

Surely that's his private medical data, not something we should ask him or his family to share.

Thanks! I won't put the details on here, but in general they were similar.Ron described some of it in his IiME talk in London. You can get the video, or look up summaries in places like MEAction, or here on PR.

 

[trishrhymes]

First update from Dr Naviaux and Ron Davis!

"Naviaux and Davis responses to Qs about Viruses and CFS"

Wow, that's so fascinating, and so kind of Dr Davis and Dr Naviaux to take the time to reply in such clear detail. Please thank them for us.

 

[adreno]

Laurel Crosby, in Ron's lab, is working on a way for patients to do this at greatly reduced cost at Metabolon. She will announce how to do it shortly.

Will there be an option for international patients?

 

[Janet Dafoe]

Wow, that's so fascinating, and so kind of Dr Davis and Dr Naviaux to take the time to reply in such clear detail. Please thank them for us.

I've been telling them both how much you all appreciate this. I think it's really important and I'm so happy to be the messenger! You guys deserve as much info as possible, and to be in the loop, and to have HOPE! You know, Whitney has no idea all this is happening. He can't communicate and he can't process even my pantomimes any more. His blood tests are so much better, but we are still looking for that key to turn on his metabolism. I can't wait to tell him how much progress has been made so he can feel that hope too.

 

[Janet Dafoe]

Will there be an option for international patients?

Yes! They are working out the shipping details now. Trying to get the cost down and keep the samples at the right temp.

 

[halcyon]

Ron Davis response:
We are conducting these direct PCR assays in the Severely Ill Patient Study, as well as extensive DNA sequencing for any as-yet-undiscovered viruses.

What is the lower end of the detection limit in copy numbers for this assay? Will you use whole blood/PBMCs or only sera for these tests? How quickly will the samples be processed and assayed after collection and what preservation technologies will you be using to ensure any viral RNA in the samples is kept intact after collection? How will you account for the possibility of an infection limited to tissue compartments where the blood is kept mostly free of virus due to the high concentrations of neutralizing antibodies that have been repeatedly demonstrated in research?

Dr Naviaux response:
Ampligen is nothing more than a form of double stranded RNA called poly(IC) for poly inosinic:cytosinic acid.

Ampligen is not poly(IC), it's poly(I)-poly(C12U). Poly(IC) does indeed have toxic effects, but poly(I)-poly(C12U) does not as far as I have read. There are many people on this drug for years at a time with no toxicity reported.

Increased IgG antibodies to CMV, EBV, HHV6, Coxsackie, etc. are not good evidence of a reactivated viral infection.

Coxsackie and other enteroviruses are tiny RNA viruses, they lack the genes to produce an episomal or other recognized form of latency as far as I understand. They are not reactivated because they never became latent in the first place.

In most of the cases of ME/CFS that I have seen where IgG antibody titers have been measured before, during, and after antiviral therapy, the antibody titers remain high after treatment, even though the patient may report symptomatic improvement.

http://jrnlappliedresearch.com/articles/Vol4Iss2/Chia2-Jar-spring.pdf

 

[Janet Dafoe]

What is the lower end of the detection limit in copy numbers for this assay? Will you use whole blood/PBMCs or only sera for these tests? How quickly will the samples be processed and assayed after collection and what preservation technologies will you be using to ensure any viral RNA in the samples is kept intact after collection? How will you account for the possibility of an infection limited to tissue compartments where the blood is kept mostly free of virus due to the high concentrations of neutralizing antibodies that have been repeatedly demonstrated in research?



Ampligen is not poly(IC), it's poly(I)-poly(C12U). Poly(IC) does indeed have toxic effects, but poly(I)-poly(C12U) does not as far as I have read. There are many people on this drug for years at a time with no toxicity reported.


Coxsackie and other enteroviruses are tiny RNA viruses, they lack the genes to produce an episomal or other recognized form of latency as far as I understand. They are not reactivated because they never became latent in the first place.


http://jrnlappliedresearch.com/articles/Vol4Iss2/Chia2-Jar-spring.pdf

I'm sending this to Ron and Dr. Naviaux for their response. It might take a while, but I'll try! Thanks.

 

[alex3619]

Coxsackie and other enteroviruses are tiny RNA viruses, they lack the genes to produce an episomal or other recognized form of latency as far as I understand. They are not reactivated because they never became latent in the first place.

On the contrary, as discussed on PR before, enteroviruses have three or four different types of latency, based on how their genetic structure changes. There is a better word than latency to describe this, but I can't think of it right now. What is not the case is that this refers to the complete original viral sequence. Specific changes are necessary, including in one form wholesale deletions if I recall correctly. @Hip might recall this better than I do, I have to go away and reread the science every time I want to talk about it in detail.

 

[KME]

Questions:

1. Given that the Lipkin et. al. finding of high cytokines in short term patients, and low after about three years, how many patients studied so far have illness duration earlier or longer than three years, and are there differences?

2. Is it possible that ME or CFS are initially high cytokine states, and then become more a dauer state if this is sustained for too long? In other words, are the hypometabolic findings found in shorter duration patients?

I was thinking the same thing, and asked the question in a much more convoluted way on the other thread a few days ago http://forums.phoenixrising.me/inde...res-of-chronic-fatigue-syndrome.46486/page-33. Hats off to your succinctness. Would love to hear from Naviaux/ Davis on this @Ben Howell! Here's how I put it:

I’m interested in how the findings of hypometabolism in this Naviaux et al study might tie in with the studies by Hornig and others in 2015 which I believe suggested upregulation of parts of the immune system in the first 3-ish years of the disease, followed by downregulation of those same parts of the immune system in longer duration disease, which Hornig described as “immune exhaustion” in longer duration patients. The Naviaux metabolomics study is on longer duration patients (mean duration of illness of male patients was 21 years, 17 years for female patients, and range of duration of illness began at 3 years for males and 2 years for females). I’d be interested to see what a metabolic study of ME/CFS patients in the first 3 years of illness would show.


Would we see a more infection-like acute cell danger response in the first 3 years of illness, switching to a hypometabolic response thereafter? Or was the response to the infection/other trigger atypical to begin with, i.e. was a standard acute CDR response just never triggered and instead we went straight into hypometabolic state? If people with ME/CFS go straight into a hypometabolic state, then in theory these people could be identified early (potentially really early in infectious onset, before they even look different from those recovering normally from the triggering infection) and appropriate advice given to try to prevent long-term disease (rest, nutrition etc).


Would love to hear people’s views on this or be directed to the answers if we already have them. Perhaps Hanson’s findings or those of the Australian team speak to this – I have not yet been able to catch up on them due to Dauer.

 

[slysaint]

Thanks! I won't put the details on here, but in general they were similar.Ron described some of it in his IiME talk in London. You can get the video, or look up summaries in places like MEAction, or here on PR.

apologies; I didn't mean to pry (didn't expect a full medical run down), was just curious.
thank-you for replying.

 

[KME]

First update from Dr Naviaux and Prof. Ron Davis!

"Naviaux and Davis responses to Qs about Viruses and CFS"

B

Profoundly grateful to Prof Davis and Dr Naviaux for being so generous with their explanations and doing this incredibly important work. When I read the Q & A, I feel calm and safe, as I know we're in the hands of expert scientists who are committed to elucidating what's going on in ME/CFS so that we get effective treatment. This sentence is like music to my ears:

"Good science needs to remain open, ask the questions without bias, design good experiments, take careful measurements, then have the courage to follow the data wherever they may lead."

This is such a nice change, it might be enough to turn off my cell danger response!

 

[Sasha]

@Ben Howell - great to see Dr. Naviaux's response! I wonder if you could break it up into much shorter paras for those of us who find big blocks of text hard to read. With things like that, I usually treat each sentence as a para, with a line gap between each.