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

[justy]

Can't wait to hear about the immune issues Ron mentioned in his post- like others here my level of hope has increased enormously by hearing about the details of their work and the high level of commitment to finding a bio marker, a treatment and a cure.

 

[Hip]

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.

I think it comes down to how you define latency. Enteroviruses don't have the usual mechanisms of latency (episomes or chromosomal integration), but do form chronic low level, smoldering infections inside cells, called non-cytolytic infections. This non-cytolytic infection may even be able to infect adjacent cells (see: How Non-Cytolytic Enteroviruses May Spread From Cell to Cell).

Because the non-cytolytic enterovirus infection is slow, smoldering but active, it's not clear to me whether you would call it a latent infection or not. Certainly in herpes family viruses, viral proteins are produced in some of the latency states, so a virus does not need to be inactive to be classed at latent.

But I don't think these herpes viruses replicate and spread during latency; whereas non-cytolytic enterovirus infections do replicate and probably are capable of spreading.

Dr Chia an others think that these smoldering non-cytolytic enterovirus infections probably play a key causal role in ME/CFS.

 

[Gingergrrl]

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.

I don't think OMI is doing this testing now either and my situation is kind of weird and I am trying to decide what to do. In May 2015 when I was in the hospital for acute MCAS/anaphylaxis up north, I had my appt with my doctor at OMI after getting released from hospital. He asked me if I wanted to participate in Metabolon for a potential future study so I donated the blood and it was bio-banked.

I asked him recently about it b/c I was very curious after the Naviaux study came out if my sample had been used. He clarified that my sample was still bio-banked due to lack of funding and that I could run the test but very expensive and probably would not lead to any change in my treatment.

But then he said it might be very interesting to run it b/c of how sick I was in May 2015 and then to run it again in the future after I have done full course of IVIG and hopefully RTX (I assume through Laurel Crosby's testing?) or whatever mechanism OMI has in place at that time.

I liked the idea of being able to compare the two samples/Metabolon tests. My only concern is whether or not the sample has been in storage too long (well over a year) for the data to be as valid in which case I do not want to run it. I asked him this question yesterday and awaiting a response.

If Dr. Davis or Dr. Naviaux know the answer (which I am sure they do!) re: how long these samples can be stored prior to testing, that will be the determining factor if I run the test versus just wait.

Thanks to you and @Ben Howell for any info that you can provide in the future.

 

[Nielk]

.

He asked me if I wanted to participate in Metabolon for a potential future study so I donated the blood and it was bio-banked.

Did he diagnose you with ME? and which criteria did he use? or did he ask you whether you have been previously diagnosed and with which criteria?

 

[Gingergrrl]

.

Did he diagnose you with ME? and which criteria did he use? or did he ask you whether you have been previously diagnosed and with which criteria?

Sorry I did not explain, I have been his patient for over two years and this was not my initial appt!

ETA: He did diagnose me with ME/CFS in 2014 but no idea which criteria he used. I am unclear re: my diagnosis now but in any case, my sample will never be used as part of any study and if I run it, it is paid for by me and will only be used as part of my own future treatment.

 

[osisposis]

it kind of seems to me that maybe those with less severe fibromyalgia may not have the brain injury of those with more severe fibromyalgia, and maybe that's why some don't see it as CNS involvement but only PNS involvement, and maybe also therefor don't see the depression involvement either, ot should I say the same areas of the brain involved there with fibro. ? is this a factor that is separating the more severe from the less severe?

 

[Thomas]

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.

That's correct. Hopefully Dr. Naviaux can confirm whether he is referring to the correct compound or not. But Ampligen is definitely not poly(IC). Also, Ampligen isn't a direct antimicrobial like Abx or Valcyte is.

With respect to certain antivirals or immunemodulators that may "delay full recovery from ME/CFS", I think a lot of us with progressive ME are more concerned about delaying the short term possibility of sliding into very severe illness. Recovery for now is just a dream. Survival is what is on my mind day to day.

What about Dr. Chia's findings of active enterovirus infections in the stomach lining of ME/CFS patients? My results and biopsy were littered with supposed active enterovirus infection. I can email results if they would like to see them. Seeing as enteroviruses could be the only type of virus that could cause an ME outbreak (due to its short incubation period, as opposed to something like EBV with a very long incubation period), I'd be interested in enteroviruses role is keeping people sick, not just causing them to be.

 

[duncan]

I was thrown a bit by the "delay a full recovery" as well.

I'm not clear that a partial recovery is on the table yet for a majority of us.

Perhaps this casual reference might be expanded on as well?

 

[Janet Dafoe]

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.

Ron says these are very interesting questions that we don't have answers to at the present time. It would be interesting to follow patients from early onset to see how the disease progresses. Again, we need funding!

 

[Janet Dafoe]

This affirms one of my thoughts, that there might be different tests for male and female patients. This will improve reliability of the tests.

PS This does not mean two different test kits, they could be combined in one kit.

Ron says it will probably be done by mass spectrometry so there won't be kits. They will do extensive analysis of the metabolites of whomever they are testing.

 

[Janet Dafoe]

Every time I visit PR I have a little nugget of hope somewhere deep down - almost subconscious - that I am going to be greeted by something special, something that will give me cause for relief and positivity about the future. The sentence quoted above encapsulates that which I am always hoping for, and I am loving every second of it.

Ron says: "I think the recent efforts by everyone are bringing more high-level scientists to work on this problem. I'm very optimistic!"

 

[Hip]

I find it interesting that enterovirus can cause chronic heart muscle infections (chronic myocarditis), and is linked to triggering heart attacks, yet there is no evidence for a higher rate of myocarditis or heart attack among ME/CFS patients, even though it is common for ME/CFS patients to have chronic enterovirus infections in their bodies (in the stomach, brain and muscles).

Could it be that this hypometabolic state is protecting the heart from developing an enterovirus infection?

When the suspected enterovirus (likely coxsackievirus B4 by my blood tests) that triggered my ME/CFS spread to over 30 of my friends and family, 3 previously healthy people had sudden heart attacks in the days or weeks after catching my virus, one of whom then went on to develop chronic viral myocarditis after the heart attack. In fact, 40% of fatal heart attacks are linked to enterovirus infections (ref: 1).

Yet heart attack and myocarditis are not found at higher rates in ME/CFS patients, as far as I am aware.

 

[Janet Dafoe]

Under Conclusions:

The study of larger cohorts from diverse geographical areas, and comparison with related medical disorders like depression and posttraumatic stress disorder, will be needed to validate the universality and specificity of these findings.

Why compare specifically with these disorders. Why not compare with MS or other?

There must be a reason these were chosen for comparison. I can speculate but would like to know their reasoning.

It's very important to be able to differentiate between diseases that are often confused for ME/CFS. Wouldn't it be nice to be able to diagnose it definitively and stop having doctors tell you you are depressed, or have PTSD or MS, when you don't? And stop having doctors tell you that your whole deal is from depression, when that is only a small part of it and actually secondary to your disease (it is pretty depressing to have ME/CFS). The effort here is to have a specific diagnosis. No more ambiguity, confusion and ignorance!

 

[Janet Dafoe]

Thanks for your post @halcyon.

After reading the paper and the comments from Drs Davis and Naviaux, It does seem like they are saying that ME/CFS is characterized by this threat induced hypometabolic state which is stuck "on". Why it is stuck "on" is unknown, or it could be like the initial kickoff of this Hypometabolic state , have a multitude of reasons why it is stuck "on". Sorting through these reasons why would be part of the teatment process.

Ron says, "Our biggest effort right now is to try to understand why it's stuck "on"."

 

[Janet Dafoe]

What is the subconscious mind?

ron says he doesn't have the technology yet to figure that out!

 

[Janet Dafoe]

Dr. Naviaux told me today that he is pretty overwhelmed with all the questions, and he's spent a lot of time on the ones he has answered. He'd love to respond to them all, but it's taking time away from his research and he needs to focus on that for awhile. I'm sure you'll be glad he's so dedicated to the research! I will continue to corner Ron when I can and get him to respond to things. I did it tonight when he was tired and wanted to go to bed, but I made him answer a couple of things. He even got funny! Hang in there everybody! He says to tell everyone "Goodnight!"

A couple of questions I find really interesting are the issue of over- vs under-active immune systems in CFS, and why patients can get better and then relapse, or get better on some supplement and then the effect goes away. Ron has some thoughts on both of these but isn't ready to have me write them down yet. Ben and I are trying to get the kernels of questions put together and prioritized. There are so many, it's a big job, but an interesting one!

 

[Hip]

or get better on some supplement and then the effect goes away.

This is something that has always intrigued me; it's almost a hallmark of ME/CFS that benefits from drugs or supplements are often temporary.

 

[Janet Dafoe]

This is something that has always intrigued me; it's almost a hallmark of ME/CFS that benefits from drugs or supplements are often temporary.

Yes, whitney has had this experience many times. Dr. Naviaux told me once something about the body reacting to the CHANGE, and once the change stops happening and everything is stable again, the effect goes away. I can't remember more specifically what he said and I am sure he said it way better than this! So don't quote me! I'm trying to find a time to ask him again so I can put it on here.

 

[adreno]

Dr. Naviaux told me today that he is pretty overwhelmed with all the questions, and he's spent a lot of time on the ones he has answered. He'd love to respond to them all, but it's taking time away from his research and he needs to focus on that for awhile

He should absolutely focus on the research. And I think he has answered the questions as well as anyone can for the time being. We must accept that several questions still cannot be answered at this time. Please let him know how thankful we are for his efforts in solving this horrible disease.

 

[alicec]

He should absolutely focus on the research. And I think he has answered the questions as well as anyone can for the time being. We must accept that several questions still cannot be answered at this time. Please let him know how thankful we are for his efforts in solving this horrible disease.

My sentiments exactly.

I am extremely grateful for both Naviaux's and Ron Davis's commitment to answering our questions but it is their ongoing research and the diagnostic and treatment possibilities flowing from it that give me a sense of optimism.