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Another negative XMRV CFS study - is this new? looks to be from CDC

Discussion in 'XMRV Research and Replication Studies' started by Jemal, Feb 22, 2011.

  1. Jemal

    Jemal Senior Member

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    I was Googling and a new XMRV study popped up. Or at least it seems new? If there's already a thread about it, sorry!

    Submission date 17 December 2010
    Acceptance date 22 February 2011
    Publication date 22 February 2011

    http://www.retrovirology.com/content/8/1/12

    Haven't read it yet, it's negative though. Looks to be from the CDC as I see 4 people mentioned with CDC e-mail addresses...

     
  2. Esther12

    Esther12 Senior Member

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    Thanks Jemal. Looks new. CDC and Cooperative Diagnostics.

    To me it looks like more of the same, but it's still adding to the evidence against XMRV.

    Apparently they used an anti-body test developed off the back of the recent monkey XMRV paper. That's new.

    At this point, I'm just waiting for the BWG and Lipkin studies. It all seems such a confused mess to me that I've given up trying to make sense of it.
     
  3. eric_s

    eric_s Senior Member

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    No idea, looks new though. Surprising, that we haven't heard about it until publication.

    Probably there won't be much new in there, but nevertheless make sure you don't miss Alter and Lo's webcast that will begin shortly. There are some people who find something.

    Someone will look bad in the end, i hope it will be Retrovirology. If they turn out to have been wrong with all those negative papers i think they can close. But you never know, we have seen stranger things happen...
     
  4. eric_s

    eric_s Senior Member

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    Aren't Cooperative Diagnostics the ones with the test that Judy Mikovits liked to call "drop of blood on a paper test" or something like that...

    Agree, it's high time this crazy story will come to an end.

    Short question, were they able to find XMRV in a real clinical sample?
     
  5. Jemal

    Jemal Senior Member

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    Yeah, it certainly looked a lot like an earlier CDC study from 2010, but it's definitely a new study. I gave it a quick glance and indeed it doesn't seem to add many news things to the table.
     
  6. eric_s

    eric_s Senior Member

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    Looks like Switzer had to round up the China department of the CDC for this study... maybe nobody else wanted to put his name under it :mask:
     
  7. Jemal

    Jemal Senior Member

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    Their patient cohort seems better described though and not a bunch of depressed people that feel tired? That kind of criticism was often directed at the CDC.
     
  8. Esther12

    Esther12 Senior Member

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    It sounded like they didn't think there were any confirmed clinical human samples. They were able to detect antibodies in 100% in the macaques (sp?) infected with XMRV for the other study.
     
  9. omerbasket

    omerbasket Senior Member

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    Esther, as it really is more of the same, it adds nothing to the evidence against XMRV.
    Bill Sweitzer is not a scientist, because if he was he would have understand that instead of trying for the second time by himself (with a company that couldn't find XMRV until now in a single clinical sample out of hundreds) to test people with unproven methods (and for the who-knows-how-many time including others who are too arrogant and would only use methods that they invented), he should have done a replication study this time.
     
  10. omerbasket

    omerbasket Senior Member

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    Short answer: No.
    Actually, in the previous study Switzer tested with a serology test 20 positives from the WPI and didn't find evidence for infection in any of them. However, that didn't got him to stop and think: "Hey, there are scientists at a place, what is it called? Oh, the "Whittemore-Peterson Institute", or even at the FDA, and NCI, who got good, clinically-validated tests for XMRV. Why won't I, in the second time I study XMRV in blood, try their tests?".
     
  11. alex3619

    alex3619 Senior Member

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    Hi, only just started on the paper but - fresh samples from 20 states. From 20 states, how fresh were they. APOBEC shuts down free xmrv rna so fast its not funny. I need to read this carefully I think. Bye, Alex
     
  12. eric_s

    eric_s Senior Member

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    This is interesting. On the other hand it does not mean they would have to find it in a human sample from someone that became sick "naturally".
     
  13. Cort

    Cort Phoenix Rising Founder

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    I don't think their shipping and storage methods were any different from Lombardi or the WPI or VPI Dx - give the blood to the lab and have them ship it overnight. That's what I did with the WPI.

    They say they used the same primers as the Lombardi papers and added some more and they were considerably more sensitive...which seems to be par for the course for every new study. USed the antibodies from the macaque study. Tests were blinded (which didn't matter in the end since they didn't find anything :))

    They do suggest that it could be present below detection limits of PCR but stated they thought this was unlikely given Lombardi et al found XMRV in so many patients with less sensitive tests. They didn't find MLV's either. They clearly don't trust the Alter/Lo paper at all. They believe the mtDNA test missed the contamination that was present. They feel the sequences are just too close to endogenous retroviruses.

    They do leave open the possibility that XMR is there - and state it might be in a much lower frequency than found in the first paper and further study is needed including coded and blinded testing by multiple labs (BWG).

    Acid Test Coming
    - this study certainly doesn't help XMRV at all but the acid test (BWG) will come when the WPI is given 60 or so samples (or whatever it is) and asked to state which ones are positive....If they can accurately pick out those - and not pick out the blood from the healthy controls then their test is correct and I imagine the entire field regroups tramps over to the WPI labs to figure out what the heck is going on. If they can't - I don't see how they can get by that...

    They should be able to do it...they've been finding XMRV in CFS patients for over a year now. Its very basic and simple test...does your test actually tell you if XMRV is there?.... and I don't see anyway you can dispute the results.....They know storage doesn't effect XMRV (much). Even if there is the relapsing remitting question - some people should have the virus in their blood - after all they found it in a considerable number of people in the first paper.

    MY guess is it's all down to the testing now. I don't think they have to get every sample right - they just need to get most of them......
     
  14. Esther12

    Esther12 Senior Member

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    Hey Cort... when are they doing that!! It's been so long, and that would have been such a good first step. Is that what the BWG are now doing?

    ta.
     
  15. Mark

    Mark Acting CEO

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    It's good news if true that this apparently definitive test - a blinded challenge to the WPI - is being done: assuming that the cohorts of positives and controls are satisfactorily defined that test can potentially nail the issue. At last. Though there are still things that go wrong and leave it inconclusive, but I'm sure you can all figure out what they are...

    Timely to reiterate a fundamental point perhaps. The WPI aren't the only people who have claimed to detect XMRV in humans. Multiple prostate cancer studies in the US and Germany (maybe more?) have made the same claim; a Spanish group have; the Japanese Red Cross did, and all found it at a few percent in controls. So i don't know how many in total, but there are lots of other groups who are saying XMRV is present in the population at high enough levels to be incompatible with any 0/0 result.

    Therefore if the WPI's XMRV results were incorrect, and XMRV is not present in humans to any significant degree at all, then it's not just the WPI's fault: there would have to be a systematic reason why this is happening. All those other groups would have to be wrong too.
     
  16. redo

    redo Senior Member

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    Yes, those are the ones.

    I am a bit puzzled by why the CDC chooses to work with them though.
     
  17. Esther12

    Esther12 Senior Member

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    @ Mark: While it's certainly possible for the prostate cancer link to hold up, but not the CFS one, it does seem like positive studies for either are linked in causing trouble for the 0/n studies. For XMRV to be linked to PC it would have to be circulating amongst humans somehow!

    I'm totally miffed by it all.
     
  18. kurt

    kurt Senior Member

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    I agree, the BWG study is important. However, I don't think we should minimize the findings of this study just because the BWG study is pending, or because people think all negative studies are somehow defective (scientifically improbable). With the variations in methods used, each study contributes a little insight into the bigger picture of what is happening. The BWG study will not be the last word either. Here are some points that stood out to me from reading through this new CD/CDC publication:

    1. They dealt with the CFS definition problem. This was the FIRST negative study to use post-exertion malaise and the Bell scale of level of disability. So very difficult to argue about this cohort.

    2. The study dealt with the regional difference problem. Another first, I believe this was the first negative study from the US that included a multi-state/area sample. That deals with regional differences.

    3. They used a stronger PCR test than the others (larger sample, 10-83x more sensitive than WPI/FDA). Also, yes, this included a gag test, which some other researchers have struggled with (Danielson in particular had to work to get their gag PCR optimized), but gag is also what WPI used with a 10x lower sensitivity, when they found 67% positive. This was a PCR test equal to the task laid out by WPI for finding CFS in a highly infected patient population.

    4. This study used 'live' XMRV samples in blood (not water) as controls (and had no problem finding those control antigens). They proved detection with live cells (VP62 and/or infected 22Rv1 cells). They validated their PCR the same way Lombardi et al did...with VP62.

    5. The collection procedure was consistent (with one noted exception) and samples were drawn specifically for the study (not banked as in many of the studies, including possibly the original WPI Science study). I realize this is no longer considered a big issue by WPI, but FWIW, this is a better approach than other negative finding studies have taken.

    6. They (CDC retrovirus group, NOT the CFS group) created a more powerful antibody test than any of the other studies to date. This approach would find evidence of ANY entrenched XMRV infection. This is a big finding, again, stronger than any of the other replication/validation studies to date. They used actual XMRV viral segments to stimulate an antibody response. This test should have had a positive finding even if the XMRV infection were entrenched in some remote area away from the blood and there was zero XMRV in PBMC (there would have still been antibodies produced after the original infection). If there was any antibody response at all, this test should have seen it, even if the virus was no longer active enough to be detected by PCR.

    While I don't think the case is closed yet for XMRV, this study is a significantly better challenge to the hypothesis than the previous negative findings. To seriously attack this study you would have to find a lot of major problems, and I just don't see them. Maybe I missed something, that is certainly possible, but I think XMRV has an uphill battle at this point.
     
  19. alex3619

    alex3619 Senior Member

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    This study was indeed much more careful. They processed most blood immediately, so there was no time for degradation. they looked for both XMRV RNA and DNA. The only weak point I could see was looking to XMRV antibodies. Most patients might not have any, but then you would think that at least some would.

    One worry that I have talked about elsewhere was raised: non murine contamination. Since XMRV could have a wide host range, contamination issues may be worse than we thought. However, and here is the kicker, I would expect to see contamination from people as likely, or even more likely, than other animals. Which again puts it in the human population. Which they again could not find. Maybe we are different from macaques, and maybe this is what is throwing out the results. Every single study is based on a series of assumptions - maybe something we have not even thought of is the issue. In that this debate might still be wide open either way. We will have to wait for the science to unfold.

    Bye
    Alex
     
  20. Cort

    Cort Phoenix Rising Founder

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    Kurt - could you go over these a bit. They used live XMRV samples as controls. How did they do this? Did they grow XMRV out of the 22Rv1 cell lines? Where did they get it from? (I'm glad you noted that the Lombardi paper validated the test using VP62 - because that was my impression reading the end of the supplemental section)

    They used actual XMRV viral segments to stimulate an antibody response. Is this statement why you believe this is such a powerful antibody test? The antibody test is an important test - I was told storage conditions have no effect on it - and Dr. Mikovits has said that is the acid test but there are different antibody tests out there. The WPI has one, Abbott has theirs, Singh has her's I believe. How do we know this is THE ONE? Do you know?
     

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