News of replication of WPI XMRV study...

[froufox]

Thanks Ross, yes looking at your other test results we are so similar! Thats interesting re the Vistide, I guess as Peterson has said himself didnt he that we CFSers have about 40-50 active viruses in our bodies at any one time so maybe it is no surprise that the Vistide was helping to knock some of the others back and maybe explains why you have done so well on it. I will be surprised if I test -ve for XMRV too, I have a feeling that I have it and if I do it would explain things as you say and certainly make things more clearcut but I think that I would rather not have it!

take care

Yes, other than the viral onset with the vaccine, we have very similar stories. High viral load CMV was obviously a big problem for me. But, Dr Peterson and I both believe the Vistide may have been suppressing some undiagnosed virus's other than the CMV because I continued to improve on the Vistide for several months after clearing the CMV. Killing other bugs, or wellness lag....who knows. But, I was negative for HHV6&7, and my EBV showed past chronic infection, but not currently reactivated (I think) CMV was my only detected infection. Lyme and it's buddies contribution to all this is definitely intriguing and may prove to have a role for many of us....Obviously does for you. Lyme is epidemic here in the Pacific Northwest too. My GP was not into Lyme at all until she moved here and began to see 100's of severely ill people with Lyme who were being refused help by anyone else. She's a wonderful person and doctor.

XMRV seems to explain a lot of this. It could explain every single confusing issue I have dealing with ME/CFS. It makes more sense than anything I have ever come across in 15 years dealing with this disease. I told Dr Peterson that, and he stopped me and said......maybe, maybe not. But I will be very surprised mine is negative. Let ya know soon.

 

[duendeni]

There are a few different figures being used by WPI. The 98% refers to the 99/101 who were found to be positive by at least one of four assays, according to the unpublished data Peterson presented at CFSAC.

The 95% apparently refers to antibodies in a different cohort (not the 101). This was in Nature News Oct. 8:




Also, this article uses a different figure-- 90/101, or 89%:

http://www.nytimes.com/2009/11/12/giving/12SICK.html?_r=1&scp=1&sq=Mikovits Whittemore&st=cse



Actually, Im wondering now if that 90 is the journalists error.

So, Im really eager not only for replication studies from independent labs, but for more published studies from WPI. Then well have more insight into the 98 v. 95 v. 89.

One concern I have is that apparently the antibody test has been used on controls, but I havent heard anything about the protein expression and transmissable virus in plasma tests being tried on controls. I worry the number of positive controls could go up, diminishing the data.

OTOH, the additional tests mentioned by Peterson raised the number of positive PWCs by 50%. If the same is true of controls, they shouldnt go above 6%--which, interestingly, is the figure found in one of the prostate cancer studies.

David S. Bell;

XMRV DNA was found from 68 of 101 patients (67%), and this was in the Science paper. That leaves 33 patients with CFS who were negative. But on further testing 19 of these 33 are XMRV antibody positive, 30 of these 33 had transmissible virus in the plasma, and 10 of these 33 had protein expression. Overall 99 of the 101 patients show evidence of XMRV infection.

http://www.facebook.com/note.php?note_id=200170205538

 

[duendeni]

Here and elsewhere it was clearly stated that the XMRV found in the CFS patients was not identical to that found in the prostate cancer samples and not identical to that found in mice. The question of lab contamination via mice was brought up when the study came out and it was settled then. These retroviruses are different!

Cecelia

Yes, here is what David S. Bell, MD, FAAP says on the matter;

c) Could some mouse have contaminated the tests by shedding some XMRV in the lab? XMRV is a big family of "simple" retroviruses. In the XMRV strains isolated in CFS patients there is a 0.3% diversity from what are carried in mice - a relatively large diversity. This virus does not vary with replication as much as HIV does. In two weeks of HIV replication the diversity is greater than 0.3%. And this is both good and bad news. Good news for the ultimate production of a vaccine. The diversity has been a roadblock in the production of a HIV vaccine. Bad news for the antiviral therapy implications. But that is way down the road.

 

[Aftermath]

Viracor

Just my $.02 that Viracor has an incredibly good reputation in this game.

Dr. Natelson used them to test my CSF for HHV-6, HHV-7, EBV, etc.

Not sure what they are doing with XMRV, but it would be interesting to know.

 

[Eric Johnson from I&I]

Thanks, Eric. Can you tell from the paper whether they used the culture for latent virus now being offered by VIP Labs?

Also, do you know what Dr. P. meant when he referred to the "co-culture technique" the Cleveland Clinic/NCI later used on 15 pts? Was this technique used in the original Science study?

Thats affirmatory on both counts. The lymphocytes were activated, which causes them to divide/multiply, prior to the culture assay AKA transmission AKA co-culture. This means activated patient lymphocytes are incubated together with uninfected cells of a different type.

Because the simple retroviruses are so simple, they can only replicate when the cell is dividing into multiple cells. Whenever the cell isnt dividing, XMRV plays it cool in the form of a provirus, which is DNA integrated into the cell's genome -- I'm guessing that is what you mean by latency.

This is what was reported in the paper and supplement, and since VIP is associated with one of the authors (Lombardi) I guess theyre doing the same sort of thing. If they change it, it would be in a way acceptable to WPI.

 

[nora_n]

About when they found XMRV, Andrea W. posted on the WPI facebook group that they found it on dec 28 in 2008 or thereabouts, it was just before newyear I seem to remember.

Viruses can change after getting into hosts, like here we have had mutated H1N1 in the most severe ill people, and those that died. But it did not infect between those patients, it happened inside the patient after infection.

About lizards and lyme, lizard blood does not kill lyme, I read a newspaper article about a scientist who had lyme himself and discovered that. The testing was faulty...I did not find the link to the article right now. I found another posting at http://flash.lymenet.org/scripts/ultimatebb.cgi/topic/1/87292?#000022

 

[Sharon Arnoldi]

comments from ViraCor on viral testing

Since there seems to be some confusion regarding the testing the ViraCor Laboratories provides, I would like to provide clarification as to what testing ViraCor performs and does not perform. ViraCor does not perform the microarray testing mentioned in the posts. Microarray testing allows for detection of many viruses into one test. ViraCor performs real time quantitative PCR testing for a single virus in each assay.

At the time the physician writes the order for a test at ViraCor, they choose which virus they would like for us to test for. For instance, a physician might write an order for HHV6 or EBV testing. We would then perform the testing specific for HHV6 or EBV. We are only testing for the virus that the physician writes the order for. Real time PCR technology cannot test for dozens of viruses at the same time and cannot detect viruses which the assay was not specifically designed to detect. At the time of this writing, December 2009, we do not have an assay for XMRV. Consequently, there is no possibility that we would have detected XMRV in any testing that we have performed.

I hope everyone finds this helpful and reduces the confusion that was noted in the previous email thread.

Sharon Arnoldi
Director, Scientific Affairs
ViraCor Laboratories (now merged with IBT Laboratories)
816-347-0113

 

[Cort]

ViroChip! WPI uses ViroChip not ViraCor. (My mistake!). I didn't even think there was another array of that type out there. My understanding was that this was the only chip of this sort. As I remember it was developed by the National Cancer Institute which I don't think De Risi is allied with.

I do remember, though, that Dr. Peterson was surprised that the chip didn't pick it up. It was supposed to have multiple genetic sequences from every virus in the world. It didn't seem to be a big issue, however - he was just surprised. We do know they've done genetic genetic tests on the XMRV from three different patients and the XMRV they found is very close to the reference XMRV type.

http://www.wpinstitute.org/research/research_basic.html

 

[kurt]

misc comments on several posts

Yet now we hear that one virus is found is possibly responsible for 95% of chronic fatigue syndrome patients. Based on what we've heard for years this doesn't make sense. Reeves definitely has a point - it doesn't appear that heterogeneous conditions can usually be tied to a virus or a pathogen. But how to make sense of this 95% number?

One way I make sense of the 95% is that part of that statistic is an antibody test for MLV and not XMRV. As I read the Science article, they used an MLV antibody in the antibody and culture testing, as a way to support the PCR testing for XMRV. I believe WPI is still looking for an actual XMRV antibody. So since MLV is related to XMRV a positive finding of 95% or 98% is only supportive of a past MLV-related infection, but not conclusive for XMRV. There are hundreds of MLV-related bugs that might cross-react with that antibody, so who knows what they found with that antibody test. Don't know if that helps or muddies the water further though.

No two people with MS have the same disease expression.
One person with Parkinson's will have only tremor but another will be plagued by dementia.
One person with HIV AIDS will remain well, another will develop Karposi.
One person with Crohn's disease will have bad episodes that are managable with medication, another will require a bowel resection.

Why should we be any different? I just don't get this.

I think this indicates that these illness are actually a type of spectrum disorder. CFS is probably a spectrum disorder, look at the different presentations and yet common outcomes.

And we are not very different, MS has its own candidate retrovirus, as does Lupus now. But that research is not very conclusive yet about whether those retroviruses are causal or passenger. Hmm, sounds about like where we are with XMRV.

Yes, here is what David S. Bell, MD, FAAP says on the matter;

c) Could some mouse have contaminated the tests by shedding some XMRV in the lab? XMRV is a big family of "simple" retroviruses. In the XMRV strains isolated in CFS patients there is a 0.3% diversity from what are carried in mice - a relatively large diversity. This virus does not vary with replication as much as HIV does. In two weeks of HIV replication the diversity is greater than 0.3%. And this is both good and bad news. Good news for the ultimate production of a vaccine. The diversity has been a roadblock in the production of a HIV vaccine. Bad news for the antiviral therapy implications. But that is way down the road.

What if XMRV is actually an endogenous virus (provirus), I wonder how that would change the diversity issue. Also, I don't see why he called .3% DNA variance a relatively large diversity. How does that compare to the diversity between different varieties of mouse, or between mice in different areas of the world? Unless you compare .3% with variation in mice I don't see how you can say it is a large diversity. If mice have that same diversity then contamination would seem more likely.

This is what was reported in the paper and supplement, and since VIP is associated with one of the authors (Lombardi) I guess theyre doing the same sort of thing. If they change it, it would be in a way acceptable to WPI.

Someone posted on CFS-Experimental that the Whittemores actually own an interest in VIP Dx, maybe through some third party. So if that is right then VIP will be doing whatever WPI says, right? Actually that is a common business strategy, to have a NP foundation combined with a for-profit business, nothing unusual there. I don't like that approach though, think it creates a conflict of interest, hard to know if what the NP does is really objective when they are connected with a for-profit company.

 

[Megan]

Thanks Sharon and Cort for clearing up the confusion re Virochip and ViraCor.

Megan.

 

[Cort]

Good point Koan - I was very intrigued by Mikes case in this regard; I have mild to moderate ME/CFS and he had about as severe a case as you can get. We looked very different; he was flat on his back wasting away.

But for me you would never know I was ill just from watching me; you would notice that I get very little exercise, that I do odd things like sleep outside, that I wake up early, that I often don't communicate verbally very well, that I take alot of naps, that I seem to a bit excitable and tense, that I talk better when I sit down, that I avoid certain foods, chemicals, etc.....

Then there's Mike - lost 70+ pounds, can't tolerate noise, light, touch, hadn't stood up for a year and a half -we seem to be very different - but what stuck out at me were some of the similarities;

• the post-exertional malaise
• the poor coordination
• the problems with over-stimulation
• the balance and vertigo problems
• the chemical and other sensitivities
• the orthostatic intolerance problems.

Take orthostatic intolerance - it doesn't appear that I have a case of orthostatic intolerance but often if I want to talk to someone at least somewhat effectively I need to crouch down. When I take the dog to the dog park I quickly sit or lie on the grass - there's a world of difference in my ability to communicate between standing and lying down.

I have my own problems with stimulation plus bad chemical sensitivities, etc. The post exertional malaise is a real standout for me. If I look closely I can see alot of similarities between this rather mild case and this very severe case.

There may very be a core problem with different subtypes branching off of it. Perhaps we shouldn't get too worried about subsets.

 

[kurt]

Good point Koan - I was very intrigued by Mikes case in this regard; I have mild to moderate ME/CFS and he had about as severe a case as you can get. We looked very different; he was flat on his back wasting away.

But for me you would never know I was ill just from watching me; you would notice that I get very little exercise, that I do odd things like sleep outside, that I wake up early, that I often don't communicate verbally very well, that I take alot of naps, that I seem to a bit excitable and tense, that I talk better when I sit down, that I avoid certain foods, chemicals, etc.....

Then there's Mike - lost 70+ pounds, can't tolerate noise, light, touch, hadn't stood up for a year and a half -we seem to be very different - but what stuck out at me were some of the similarities;

• the post-exertional malaise
• the poor coordination
• the problems with over-stimulation
• the balance and vertigo problems
• the chemical and other sensitivities
• the orthostatic intolerance problems.

Take orthostatic intolerance - it doesn't appear that I have a case of orthostatic intolerance but often if I want to talk to someone at least somewhat effectively I need to crouch down. When I take the dog to the dog park I quickly sit or lie on the grass - there's a world of difference in my ability to communicate between standing and lying down.

I have my own problems with stimulation plus bad chemical sensitivities, etc. The post exertional malaise is a real standout for me. If I look closely I can see alot of similarities between this rather mild case and this very severe case.

There may very be a core problem with different subtypes branching off of it. Perhaps we shouldn't get too worried about subsets.

Cort,
That is an interesting analysis of similarities between two PWC in a different 'subset'.

Your list reminds me of Teitelbaum's mantra that there is a broken HPA function in all PWC. For instance, a disturbed hypothalamic function can account for inability to maintain homeostasis in any abrupt change, such as noise, exertion, post-exertion, change in posture, or problems adapting to strong smells, problems with stress response, taste and food sensitivities, etc. And the hypothalamus even governs weight control (gain or loss), the sleep-awake cycle, energy balance, fatigue signals, and immune-detox cycles.

But what is disturbing the hypothalamus?

Maybe the 'subsets' of CFS are just the different ways the HPA system can be disturbed. And maybe the different ways that some PWC have recovered or put their symptoms in remission reflects differential treatment of their personal HPA disturbance.

 

[Marylib]

What's bugging the hypothalamus?

But what is disturbing the hypothalamus?

Infection.

 

[richvank]

To kurt

Hi, Kurt.

But what is disturbing the hypothalamus?

I think the problems with the hypothalamus in CFS can be accounted for by glutathione depletion there. We have good lab evidence for glutathione depletion in CFS, and it is known that the brain has a very meager ability to convert methionine to cysteine, so the brain is one of the organs that goes low in glutathione first when the body has a problem with it systemically.

Rich

 

[Michael Dessin]

Rich

What comes first then...Glutathione depletion or infection??

Mike

 

[Marylib]

Which comes first?

What comes first then...Glutathione depletion or infection??

Mike

Yeah, what Mike just said

By the way, Rich am trying your protocol and appreciate all you are doing to help us.

 

[duendeni]

What if XMRV is actually an endogenous virus (provirus), I wonder how that would change the diversity issue. Also, I don't see why he called .3% DNA variance a relatively large diversity. How does that compare to the diversity between different varieties of mouse, or between mice in different areas of the world? Unless you compare .3% with variation in mice I don't see how you can say it is a large diversity. If mice have that same diversity then contamination would seem more likely.

Hey, Kurt, I hope you will forgive me for any slippages/my ignorance here as I'm an English literature student with no scientific background (apart from biology A level and my self-education on CFS, that is) but I believe Bell referred to 0.3% as a large diversity from the endogenous virus (Xenotropic MLV) because XRMV is a simple retrovirus with very few cycles of replication. There was something like 0.1% diversity between the CFS XMRV patients and the prostate cancer XMRV patients. Also, I think its pretty unlikely that the virus in the study represents a provirus because of the "phylogenetic" relationship that Dr.Peterson mentioned. John coffin confirmed this is his CFSAC tesimony.

 

[fresh_eyes]

What if XMRV is actually an endogenous virus (provirus), I wonder how that would change the diversity issue.

George, who understands these things, pretty well put this possibility to rest in another thread - it's definitely not endogenous. Though it could possibly be activating other endogenous retroviruses.

 

[Megan]

Control Groups in Replication Sudies

Hi all, following some of the discussion on this thread, I am wondering if when the replication studies come out the most important thing for us to look at initially is the results are for the control groups.

I am thinking this because there seems to be so much controvery about how the CFS groups are selected and whether we all have the same illness or subgroups etc. that it may be differerent to interpret different results from different studies if they have selected their different cohorts differently.

On the other hand there should not be as many of these issues to cloud the research on controls, so long as they are 'non contact' controls. I understand that there can still be regional differences in controls and that they would need to be age and sex matched etc. but with the very low rate found by WPI in the healthy population you would expected that this would have to be relected in some way in other studies if the WPI research is correct. I would think therefore what is found in controls may be initially the most important indicator in relation to the WPI testing methodology methodology and findings.

I also have not seen anything released from WPI about antibodies in the control groups compared to CFS cases. This seems odd to me. Surely the level of exposure in controls measured by antibodies would have to be higher than PCR alone. It could reduce the argument for XMRV as a cause of CFS if positive antibodies were found at high rates in the healthy population.

Also, if other studies look at what groups have the virus we would hopefully get a much better sense of how the virus is transmitted.

I would think the studies being done by the agencies responsible for blood safety (supposedly doing thousands of samples), talked about on another thread, might be important in all of the above.

Thoughts anyone?

Megan.

 

[usedtobeperkytina]

I never

I never have bought into the "subgroups" theory.

I say that if we have the XMRV virus or have antibodies, we have XAND (formerly known as CFS). Now, we can have it mild, medium or severe. We can have more severe symptoms in this area and not so severe in another area, but another XAND patient may be reversed. I think that because this involves so many different body systems, we all will have different symptoms. That does not mean we have different diseases. That means our bodies respond differently to the XMRV, based on many factors.

I think some of us have active XMRV infection. I think some of us have damage, causing mild, medium or severe symptoms, from a prior XMRV infection.

But, now, I do think Fibromyalgia is also XAND, but with a much different set of symptoms (the rotating sharp pain and sensitive points) which reflects another level or different representation, if you will, of XMRV infection or post XMRV infection.

Basically, XAND / CFS is when the virus damages the immune system causing a downward spiral that is hard for the body to recover. And Fibromyalgia is XAND affecting mostly the nerve chemical response, damaging that system.

Call this the Tina Hypothesis.

Tina