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Hunting down the cause of ME/CFS & other challenging disorders - Lipkin in London
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New Amy Dockser Marcus blog re XMRV Working Group Report

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by RustyJ, Jul 26, 2010.

  1. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Amy has blogged about the upcoming XMRV Working Group Report to the FDA.

    http://blogs.wsj.com/health/2010/07...e-to-hear-about-xmrv-working-groups-research/

     
  2. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Seems to suggest that the CDC labs have been looking for the wrong virus up till now which would explain the negative results. In other words no one bothered to use WPI's samples ... didn't bother, didn't want to, or never in a million years. At least WPI seems to be driving this effort.
     
  3. shrewsbury

    shrewsbury member

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    Here's what they'll be talking about today
     
  4. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    No one care to comment? This is really solid important news. Real bricks and mortor stuff. From here will come definitive unchallengeable facts which will underpin all future progress on XMRV.
     
  5. floydguy

    floydguy Senior Member

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    I agree it's solid and interesting. I just don't know what to make of it. There seems to be so many contradictions that it's hard to follow what's what.

    I was particularly interested in the maybe we should see what's going on with actual people (that have XMRV presumably). I wonder where those people will come from.

    I am grateful this journalist is staying on top of the issue and I feel so far that she is providing good information. I hope that continues...
     
  6. Sasha

    Sasha Fine, thank you

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    Thanks for the link, RustyJ - I've posted a comment on Amy's blog expressing my appreciation for her continuing to cover this. I'd like to encourage others to do this too - it's important that we show our appreciation, I think. We're very lucky to have her attention and to have her keeping the XMRV story in the public eye. You don't have to register or give your email or anything to make a comment.

    I wish I knew how to comment on the actual content, RJ! The implications are beyond me. I hope one of the bioscientists on the board might have something to say!
     
  7. usedtobeperkytina

    usedtobeperkytina Senior Member

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    So this is about finding out if in blood supply. That is all well and good, certainly needed.

    But for those of us who are sick and not giving or accepting blood transfusions, sure would be nice to have a standardized test that is approved by FDA and paid for by insurance.

    I don't see any mention of this in her article. But I thought this working group was going to produce that.

    Good to know phase 1 is complete with all able to detect some of the virus.

    Good to know they may be closer to understanding the difference between finding it in stored blood and live people.

    This reminds me of the Defraitis virus where you can't find it if it has been frozen.

    Tina
     
  8. parvofighter

    parvofighter Senior Member

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    Will the winning assays be made avaiilable for clinical use?

    1) When will a standardized methodology/assay be available for the real world?
    So the Working Group is putting together reference panels (analytical and clinical) against which the 6 labs will test their XMRV detection methods and assays. Anyone able to comment on the potential availability (and timeline) of the clinical panel - and then the standardized assay/methodologies- to the "real world"?

    2) Good news - we've got at least some competent labs formally establishing clinical panels and assays.
    It give me no small measure of comfort that the Working Group is turning to the WPI for "biospecimens from blood donors, patients with Chronic Fatigue Syndrome whose blood was previously found to be positive for XMRV by the Whittemore Peterson Institute"... as opposed to, say, using biospecimens from some of those quasi-scientists bizarrely featured in Abbott & Costello's comedy this fall, who have proven their inability to find XMRV. (And no, of course I'm not speaking of the likes of Ruscetti, who are doing a great job of saving our bacon.) It's also a relief to see that several labs who know how to find XMRV (eg. WPI, FDA, NCI) are on the Working Group.

    Now remember Alter's talk from way back, when he commented on 2 separate labs validating the Science findings? I understood that to mean that the NIH and FDA had separately found XMRV... now it looks as though it may not just be the NCI/NIH but also two separate FDA labs... even better?

    If I'm not mistaken, the CDC folks involved in this Working Group will be facing some formidable pressure from their peers at the NCI/FDA etc to learn how to actually find XMRV. This is a good thing.
    From the Blood Products Advisory Committee materials:
    http://www.fda.gov/AdvisoryCommitte.../BloodProductsAdvisoryCommittee/ucm218968.htm

    Evaluation of Transfusion Risk in the US:

    Transmission through transfusion has not been shown, but is theoretically possible since virus has been detected in blood cells and there is evidence of cell-free virus. A seroprevalence study in Japan found 1.7% of random donors to be positive (12). Preliminary studies have shown that 3/2851 US blood donors (0.1%) were anti-XMRV antibody positive using a research immunoassay based on gag and env proteins (5).
    A Blood XMRV Scientific Research Working Group, led by the National Heart Lung and Blood Institute (NHLBI), has been established to identify and design research studies to evaluate whether XMRV poses a threat to blood safety. An evaluation of blood safety risks includes 1) an evaluation of the prevalence of XMRV in blood donors; 2) if prevalent in blood donors, a determination of whether the virus is transfusion-transmitted; and 3) if transfusion-transmitted, whether clinical manifestations occur.

    An evaluation of the prevalence of XMRV in blood donors necessitates a way to measure or identify the agent in blood specimens. The fact that different laboratories obtain different results for XMRV detection in patients specimens and different prevalence estimates in normal controls strongly suggests the need for the development of standard XMRV reference and clinical case and healthy donor prevalence panels for XMRV detection. Thus, development of XMRV nucleic acid test (NAT) analytical and clinical panels was identified as the first priority by the Working Group.

    As a first step towards this goal, an analytical reference panel was developed to validate NAT assays for use in donor survey studies . The panel was developed by the Blood Systems Research Institute which is the Central Laboratory for the NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II). Virus stocks were prepared from culture supernatants of the chronically infected prostate cancer cell line, 22Rv1. Following titration, reference infected cell preparations were established by spiking known numbers of infected cells into whole blood. Similarly, reference infected plasma preparations were established by spiking pedigreed-negative plasma with known viral titers of cell-free culture supernatants at serial dilutions.

    These coded analytical reference panels of specimens containing varying concentrations of XMRV virus as well as clinical panels which include biospecimens from blood donors, patients with Chronic Fatigue Syndrome whose blood was previously found to be positive for XMRV by the Whittemore Peterson Institute, and positive and negative control specimens are in the process of being tested by up to six participating laboratories to compare the sensitivity of their respective assays for XMRV. The study participants include laboratories from the NCI, FDA (two laboratories), CDC, Blood Systems Research Institute and the Whittemore Peterson Institute.
     
  9. Esther12

    Esther12 Senior Member

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    Thanks for the link. Nice to know things are progressing (slowly).
     
  10. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    There is a lot more in this article than FDA's inaction on the blood supply:

    CDC Labs involved and finding virus
    This is a crucial point in Amy's blog. Not just separate FDA labs found the virus, but it seems CDC labs have found the virus. THE CDC LABS HAVE FOUND IT. You will recall the CDC just releasing a study where they did not find it. Well now their own labs are refuting this study.

    Still some confusion about the virus
    What virus were the earlier studies looking at? Is the prostate XMRV really that different? What this seems to say is that WPI's patient samples were deliberately ignored. The CDC in particular didn't even bother to check whether there positive controls were the same as those the WPI had sent.

    Legitimising and standardising testing
    Also the thrust of the article is not so much about the blood supply as far as I am concerned, but about legitimising and standardising testing. People are disappointed about the FDA's apparent lack of action, but should be pleased that WPI is progressing efforts to standardise testing. Once that is done, our other concerns will become less important.

    Moving on to symptoms
    Once testing has been standardised, the debate will move on. It won't be about whether its in ME patients or not, it will be what does it do in ME patients. This is an important step up. This is what we should be excited about.


    Blood supply not in peril
    Do not be too upset about the FDA's inaction on the blood supply. The blood transfusion thing is really a minor issue. Not many ME sufferers are going to give blood. Our angst about blood transfusions was really about getting recognition, not danger to the blood supply.
     
  11. Sean

    Sean Senior Member

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    Yes, and yes.

    This is the main game right now and the most important thing for us, getting a standardised, reliable test. Everything else will flow from that. The science (and scientific politics) has moved past the issue of the existence of the virus, and into how do they detect it reliably, and hence determine its prevalence and correlation with various disorders.

    •••••

    Perhaps the other message to take from all this is that the CDC no longer run the show, and indeed are under serious pressure from the real scientists. Which is fine by me.
     
  12. SOC

    SOC Senior Member

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    Yes, and then again, maybe no.

    Amy said,
    [my bolding]

    We don't know anything about the amounts of XMRV in the samples, or what "at least some amount" means. Say, for example, one sample was heavily spiked with XMRV and that's the only one some test (maybe the CDC's) could find? That doesn't mean they have a snowball's chance in heck of finding XMRV as it exists in a normal human blood sample. A person with no sight, hearing, or sense of smell could still find an elephant in their kitchen. (Or recognize when a train is barrelling down upon them).

    Sounds like a carefully worded face-saving statement to avoid embarassing some lab(s) whose performance in phase 1 was pretty dismal. But maybe I'm just getting cynical....

    Or, from another perspective, the fact that they can find XMRV in these samples only reinforces their claim that they know how to find it and there wasn't any in the "CFS" patients they tested.

    I'm not sure that, at this point, I give a flying fog how the CDC performs in this process. Well, maybe I do... I'd probably be happiest if their performance was sufficiently pathetic they get sidelined from the whole XMRV research field. A girl can dream, can't she...?

    I still have a lot of questions about this process, but I'm extremely glad it's progressing well.
     
  13. dsdmom

    dsdmom Senior Member

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    Maybe I'm not looking at this the right way but it seems to me that if the CDC CAN find xmrv, that's not necessarily a good thing. They can say "See, our study was right - we can find it, it just isn't present in cfs patients."

    I whole heartedly disagree with this statement. I think it is extremely important that this is addressed. Although we are waiting on test results to be 100% positive, it is most likely that I got sick from a transfusion. so please don't say that the transfusion thing is a minor issue. It is a HUGE issue for people who get sick from them. I'd say there is a danger in the blood supply - and that it's not just about getting recognition.
     
  14. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi dsdmom. I worded my response clumsily. I am sorry you may have contacted XMRV from the blood supply. I did not mean to diminish the potential danger. I was trying to point out that if the FDA ignores the blood supply danger, it is not the end of the world. We need to concentrate on the positives aspects of what Amy has written about and what they mean for our future.
     
  15. dsdmom

    dsdmom Senior Member

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    Sorry if I got a little worked up - it's obviously just very personal!
     
  16. parvofighter

    parvofighter Senior Member

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    Still not clear on process to develop standardized testing for CLINICAL use

    Can anyone help out on this one? When will tests be available for actual patient use?
    I'm still not clear (as per post #8) if/when the "winning assay(s)" to detect XMRV will be made available for clinical use. Keep in mind the terms of reference for this Working Group are ultimately focused on safety of the blood supply, not acceleration of access of diagnostics for patients. So my question remains: what is the process proposed (if there is one at all) to translate what this working group learns into bona fide tests available clinically? What is the process to approve and licence the tests (eg. FDA-approved), so that insurers will cover it, and other countries will adopt it? I am not at all certain whether the finding of a validated test automatically translates into its availability on the market. Does anyone know how long will this take? And how does this tie in with VIPDx plans for availability of the XMRV serology test?

    Clinical vs analytical panels
    Perhaps one of the sources of confusion is the discussion of clinical panels vs analytical panels. These panels are merely an array of samples of XMRV - the clinical ones blood from "real" infected patients; the analytical ones "spiked" normal blood or water with designated amounts of XMRV, against which the various labs will test their detection assays. An important differentiator for the real world is whether a lab can detect XMRV in a clinical panel (a proxy for a patient) - and what their detection threshold is. The CDC may well be able to detect XMRV in spiked analytical samples. But when presented with a sample of unstimulated blood from a bona fide ME/CFS patient, they may miss the elephant in the room with their assays. I totally agree with Sickofcfs that some face-saving may well be taking place with the Working Group's carefully worded line: "All the labs were able to detect at least some amount of XMRV". What is unsaid is that some labs (hazarding a guess here - the CDC?) may have to be hit over the head with XMRV to find it.

    What are the rate-limiting steps before we have an available CLINICAL XMRV test?
    Which brings me back to the crux of the matter. What are the steps before a validated test for blood safety purposes is translated to an available clinical test for us patients? I am not at all certain that a validated test for the Blood Working Group = a validated test for clinical use. Presumably we have to wait for patent processes, licencing and some commercialization. FDA approval? Other hurdles? How long might that take?

    Blood safety remains a HUGE issue
    I agree with RustyJ that blood issues have unwittingly raised the profile of ME/CFS. But I also agree with dsdmom that blood safety remains a huge issue for ME/CFS patients. If those 3-7% figures hold up, we are looking at a crisis of mammoth proportions in both the availability and safety of our blood supply.

    I kind of think of it as the larger issue of preventing transmission of an infectious retrovirus that simply devastates our lives, by any means. Just how vigilant do we need to be to spare our loved ones the painful journey of ME/CFS? Does food preparation connote danger? Given the infectivity in cluster outbreaks of ME/CFS, and the finding of XMRV in respiratory secretions, is this retrovirus THAT infective (eg. via respiratory droplets... coughing, sneezing)? Or are cluster outbreaks the result of infectivity of an opportunistic virus (eg. EBV). While there are some people out there who might benefit spiritually from contracting XMRV, I frankly wouldn't wish it on my worst enemy.

    And what about when we ultimately get antiretrovirals (if indeed XMRV is "it), or possibly B-cell depletion therapy or other means to eliminate viral reservoir. How readily might we re-contract XMRV - recognizing that retroviruses are embedded in our genome? Will immune modulating therapy render us "immune" to re-infection? Could massive re-exposure cause an XMRV relapse? What measures do we need to take to prevent re-infection?

    Also, look at where our population is at age-wise. The boomers are flocking to cardiologists en masse to get bypass surgeries... all of which typically require blood products. And at the end of the day, all of us are vulnerable to sudden trauma - and the possibility of a need for blood transfusions. I'm with the vampires... blood issues for ME/CFS and XMRV remain extremely important - to us patients, our loved ones, and the community at large.
     
  17. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    The vast majority of those with XMRV contracted it by means other than blood transfusion. Extrapolating from this, XMRV will be pervasive in the general population via these other means long before it becomes a critical issue in the blood supply. While those who contract the virus through the blood supply represent a personal tragedy, the rapid spread of a contagion via sneezing, or sexual contact without any real measure of control is the real threat by some orders of magnitude.

    Nothing unwitting about it. It would be disingenuous if the general ME community did not acknowledge that it saw the blood issue as an opportunity to raise the profile of the disease. I certainly did.
     
  18. bakercape

    bakercape Senior Member

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    Well we should be upset!

    Don't forget not everyone with XMRV is symptomatic! Like HIV a large percentage of people will be carriers and not sick! So don't tell people to not be upset.

    Also I'm sure many have gotten CFS or prostate cancer from a transfusion. SO it is a MAJOR issue!
     
  19. Sean

    Sean Senior Member

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    As I understand it, anti-virals never clear retroviruses completely, just suppress their activity. IOW, we will probably be taking them for life.

    Given that, it seems unlikely that re-infection is going to be an issue for those already infected.
     
  20. parvofighter

    parvofighter Senior Member

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    I think we're (mostly) in agreement

    Hey RustyJ, I don't disagree that the ME/CFS community has knowingly benefited by intelligently leveraging real blood issues. However as a stand-alone community, our advocacy doesn't count for much (yet). What HAS made a huge difference are the prominent scientists and mega-pharmas who have indeed been unwittingly pulled in to ME/CFS research, as a result of RNase-L connections, lymphoma connections, etc., and that's what I was addressing. They're concerned about the blood supply too, and that has inevitably - and unwittingly - pulled them into ME/CFS research. Nothing disingenous about that.

    I'd rest with my comment that the blood supply and safety remain a huge issue. If as many as 7% of potential donors have XMRV, this has MASSIVE implications for the supply of safe blood - at least in North America, where processes such as the Cerus Intercept system are not in use to deactivate XMRV. There is already a critical shortage of blood products. Factoring out a whopping 7% of donors would have a huge impact on blood supply.

    As for XMRV contagion, the jury is obviously still out on that one. HIV is found in saliva, but not transmissable by kissing. And we don't know yet whether the ME/CFS outbreaks are a result of the opportunistic infection activating a pre-existing XMRV - or a bona fide new XMRV infection transmissible readily by respiratory secretions. Bottom line Rusty, I suspect that while we have different perspectives on the blood supply, we are in agreement that all methods of potential transmission need to be judiciously addressed.

    But I still want to know - from anyone - how long do we have to wait for a clinically-available validated XMRV test?!!!
     

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