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The Chronic Fatigue Initiative and Interview with Mady Hornig
In a follow-up article to the recent IACFS/ME conference presentation in San Francisco, and after speaking at length with Dr. Mady Hornig, 'searcher' delves deeper into the impressive work being completed by the Chronic Fatigue Initiative, and focuses in on those cytokine results ...
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Telebriefing is up and available to listen NOW: 5 pm EST

Discussion in 'XMRV Research and Replication Studies' started by Rrrr, Aug 23, 2010.

  1. Sunshine

    Sunshine Senior Member

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    Hi. The CDC study didn't use a known positive sample of XMRV and they did not use the sample the WPI sent them that was known to be positive! Without having a known positive sample the CDC study of negative association of XMRV in CFS is unfortunately invalid, because the CDC are not sure their assay even works before being able to 'find' any MULV/XMRV in CFS patients. How the CDC XMRV/CFS paper was even published is unclear as it fails the most basic rigours of the scientific method of undertaking a study and that is knowing what they are comparing against, with no positive sample this was not possible, additionally the CDC was not even a replication study using the same cook book of methods to detect XMRV.

    Suzanne Vernon Phd (of the CFIDS Association of America) said that the CDC paper on XMRV was so poor she commented: ''“ the explanation for not finding XMRV in these samples is simple – this was a study designed to not detect XMRV using a hodge-podge sample set. “

    All other negative studies of XMRV in CFS also have also never replicated the SCIENCE paper methods that Lombardi et al used to detect XMRV in CFS, thus also invalidating their ablity to find XMRV in CFS patients by default. The fact is no one using the same method of Lombardi et al in the SCIENCE paper trying to find XMRV in CFS has yet failed to discount what the WPI found, that is very important for people to know.
  2. LaurelW

    LaurelW Senior Member

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    Does this mean it can make you sick again in a whole different way after it has mutated quite a bit? Would this explain the relapsing/remitting nature of the disease? Do we end up carrying a whole bevy of mutations (the original and all the changes) like a walking stew of disease?

    I just listened to the journalists' teleconference, and I haven't yet heard anybody ask (there or elsewhere): since some variants are polytropic, does this mean we can still get it from mice? :eek:
    (Hello, Hantavirus!)
  3. usedtobeperkytina

    usedtobeperkytina Senior Member

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    hmmm, makes me think about the stages many associate with the illness. I thought it might be because of virus moving around to different parts of body.

    Maybe contributing factor is mutation.

    Find it interesting that they report mutations, while Science article showed little mutation. Remember Coffin spoke about that at CFSAC?

    Tina
  4. Rrrr

    Rrrr Senior Member

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    excellent questions, laurelW!!!

  5. LaurelW

    LaurelW Senior Member

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    Thanks. No more cleaning out sheds without an N-90 respirator for me. Oh wait, I can't do that anyway!
    :In bed:
  6. Dorothy

    Dorothy

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    I just finished reading (or trying to read - most of it is WAY over my head) the actual FDA/NIH PNAS article - interesting that on page 6, the authors say that "In sum, none of the four studies that have failed to confirm the PCR evidence reported by Lombardi et al., nor our own study, has attempted to fully replicate that study". Would have been nice if they'd actually done that! At least in the press conference, they did mention that the WPI had gone way beyond the FDA/NIH by finding an entire virus (XMRV)and then showing that it could infect other cells. This ought to be a great boost for WPI's credibility.

    I have to admit, I cringed when Steve Monroe's voice finally came on over the telephone - I was hoping he'd just keep his mouth shut the whole time!!! It beats having to listen to Reeves though. :)
  7. Mark

    Mark Acting CEO

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    Yes that's really quite odd, they were suprised it had mutated so little and thought that meant it had jumped recently. Now I read that it probably jumped species 100,000 years ago!

    The genetic identity was only based on 2.5 sequences though, so presumably they happened to sequence the oldest samples?

    If that's the explanation, then the samples they sequenced might have been the oldest ones and the strongest reactions they got - ie. the ones closest to 'true XMRV' therefore - but even so, that implies those samples were close to "ground zero", which in turn implies that these viruses mutate really fast.
  8. OneWaySurvival

    OneWaySurvival

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    A few highlights from NIH/FDA telebriefing - Aug. 23, 2010

    The first few minutes was a summary of the paper and background on XMRV in CFS, given by Dr. Alter.

    Then questions came in from the media for another 30 minutes or so. Most of my notes, however, are from the 1st segment.

    Dr. Alter made a lot of interesting points that gave strength to the WPI findings. I found myself being very grateful for him and his defense of the WPI research. Some highlights from his summary:

    * "[Given the findings of XMRV and its related variants] A better term is Meurine Leukemia Virus-Related Viruses, which emcompasses XMRV"

    * They found a "Dramatic Association" (yes, he used the word "dramatic"): 86% in PWC's vs. 6.6% of healthy blood donors.

    * "Have not [yet] proven causality....many many more pieces to fulfill"

    * Confirms findings of WPI's Science Paper (later he amended his comments during the reporter segment to say Highly Confirmatory!, and also admitted that the WPI's research is more advanced because they have already cultured the virus in patients as well as having found antibodies in patients, which the NIH said was not part of this study, but they're working on it.

    * Dilemma as to why CDC found nothing, time is simply needed to work this out

    During the Q&A, I jotted down the following:

    * A 2nd FDA guy (not Dr. Lo), responded to a question about whether there is currently an FDA approved test. He said (paraphrased) XMRV working group is tasked with solving standardization and validation issues for assays; but until then "no FDA Approved test is ready at this time", only assays used in the research setting are ready right now

    * Dr. Lo gave a very good, simple explanation of the difference between polytropic and xenotropic (the difference between the polytropic MLVs they found and XMRV). He said a Polytropic retrovirus is able to infect mouse cells in additon to non-mouse cells (other animals), whereas Xenotropic can no longer infect mouse cells...it can only infect non-mouse cells. He went on to say that this actually strengthens or extends the WPI findings, because it is more characteristic of how other retroviruses work.

    * Dr. Lo (or Alter, I can't remember) said another reason this Polytropic finding was important is that it gave them confidence that they were dealing with a real family of retroviruses and not a lab contaminant. Paraphrasing still: Because they found several mutations in patients, not just a single strain (like in the Xenotropic model), this makes the retroviral infection theory much more plausible for CFS. It's how other retroviruses behave. He said the WPI has since found more than one strain also (since the Oct. Science paper), so they are in agreement about that.

    * Dr. Alter is currently doing another study testing 1000 blood samples to help solve the transfusion link by looking at frozen banked samples of known blood recipients. Data will be available soon. (He was saying it in the context of how to move the state of knowledge forward, so I got the feeling it was going to be good news...but I obviously don't know)

    * Good ol' Dr. Steve Monroe from CDC was mostly silent on this call (as was humorously pointed out by Recovery Soon), but the couple of times Monroe did speak, it was classic CYA mode. It was transparent. The one quote I wrote down from him was that the CDC found zero XMRV or related MLVs in CFS [or healthy controls I might add], but he was oh so gleeful to add that they did find some in prostate cancer. You could almost hear him sweating bullets, and I think he was praying that answer would put all our minds at ease, once and for all. :rolleyes:

    * One of the authors (or the 2nd FDA guy, I can't remember) concluded by saying that future studies, especially within the XMRV working group would be aimed at 1) causality and 2) vector of transmission

    I sure hope the media can read between the lines and tell the accurate story here. Why did none of the reporters latch on to the reality that 4-7% of the healthy population have a dang retrovirus?!!!? and ask some hard-nosed follow-up questions? Here's hoping they will ask those questions soon since they missed their chance on this telebriefing.

    No mistake about this, though: This NIH/FDA paper (which is already almost 5 months old!) is a huge step forward!

    Now I guess it's back to waiting for the NEXT positive papers that are supposedly coming out soon. Maybe some good stuff in time to be discussed at the Sept. 7 & 8 XMRV conference?
  9. Esther12

    Esther12 Senior Member

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    Isn't it more likely that the samples they sequenced were just coincidentally very similar/related?

    It is all a bit of a mystery though.
  10. Trooper

    Trooper Senior Member

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    Genius! - This has totally made me : )
  11. Otis

    Otis Señor Mumbler

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    Would be interesting to know where/when these samples were taken. Both factors would appear to be increasingly importent given what I've been able to glean out of today's news.
  12. Sing

    Sing Senior Member

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    Here is the point I got on the variability of sequences in this family of retroviruses. Dr. Lo said this is typical and expected for retroviruses which "make bad copies" of the RNA all the time using their transcriptase--or is it, reverse transcriptase--system. So small changes could be made with each/any replication. And still the retrovirus in its variations can produce the same disease. They see this all the time with other illnesses.
  13. Sunshine

    Sunshine Senior Member

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    Firstly, thanks so much for your lengthy and informative write up of the audio chat most of us cannot hear. Well done.

    To add some thoughts to your last comment I quoted above, there are two studies that surely will be released soon.

    1) Replication study of XMRV in Sweden (Blomberg & Gottfries) - http://www.meresearch.org.uk/research/projects/xmrvsweden.html
    2) Study/Data of XMRV in UK patients (Mikovits)

    Here's hoping these studies bring positive news. We do know there is XMRV in the UK from members of this forum, but it's not official thanks to Wessely & McClure and UK CFS/ME charities discouraging people from getting tested. Indeed UK CFS/ME charities and not even letting members know the can even get tested at VIPDX in America and REDLABS in Belgium. :worried:

    I sense Mikovits to the rescue......:victory:
  14. Mark

    Mark Acting CEO

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    To expand on what I suggested above...

    The WPI testing that reached over 90% positive through multiple techniques must have been picking up all the other MLVs as well, making it consistent with Alter's findings.

    If it was picking up the other MLVs too, but was fundamentally based on the 'reference' XMRV code, then a small few of their samples would have been much closer to 'true XMRV' than the others, and those would have given the strongest results on their PCR tests.

    So when choosing which samples to sequence, it's likely they would have chosen the ones with the strongest match - and those would be the "true XMRV" samples.

    Thus the ones they actually sequenced were the true XMRVsamples.

    I reckon my theory is a better explanation than coincidence. What they sequenced was 98% identical to the known XMRV strain, but if Alter couldn't find any actual XMRV at all, then it would be a huge coincidence for them to have chosen the "true XMRV" sample to sequence. It's also implausible that their study population all had "true XMRV" when Alter's population showed more diversity.

    The only thing that makes sense to me is that they were looking for XMRV, so they chose the samples that gave the strongest results to sequence fully. Unless someone has a better explanation...
  15. vdt33

    vdt33

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    I listened to the teleconference and this is what I got from it. First, Lo and Alter both agreed that their research strongly confirmed and strengthened Judy Mikovits research.

    They used a PCR that detected mutations of the retrovirus (variants) in the samples. So there is more than one variant of it in a person with CFS.

    Next, since they found that some variants of this retrovirus in samples infect both mice and humans (polytropic variants), the term XMRV is no longer accurate because the X for xenotropic means a retrovirus that does not infect its source (mice, in this case). But XMRV is *one* of the variants they found in samples. What they found encompasses XMRV. So it is true that they found XMRV.

    They are now using a term that includes both xenotropic and polytropic variants of this retrovirus (MLV related virus).

    The CDC was trying to save face, and Alter and Lo were trying to help them save face.

    Most of the media didn't do a very good job of covering the telebriefing.
  16. usedtobeperkytina

    usedtobeperkytina Senior Member

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    another name controversy?

    I don't know if I could take it.

    Is it HGRV? Is it MLV? Is it PMLV? Or is it XMRV? Or (aghast) is it Xenotropic Murine Leukemia Virus-related Virus-related Viruses? XMLVVV?

    Tina
  17. citybug

    citybug Senior Member

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    This interview was such a good overview of the NIH paper. I hope someone can transcribe it. It has more information than the newspaper articles while being less technical than the paper, and won't be available elsewhere.

    They had really good samples from Komaroff. That they preserved very well.

    It sounds to me like they had a different technical approach from WPI. WPI was testing several different ways, and culturing the virus, so they were looking at infectiousness. After their paper they started sequencing. Lo might have different technology, or database and he went to looking at sequences first. So they are complementary.

    I was also thinking their definition -non xenotropic implies can get it from mice, which clears up some of the mystery of how the virus got here.

    Monroe was better than I expected. He didn't deny the association with MECFS. The work he described that needs to be done is all serious research that does need to be done for us. Even by saying they did find it in prostate cancer, he is confirming the link between
    MULVs and human disease.

    At the end Alter or Lo was talking about the low copy number.
  18. SOC

    SOC Moderator and Senior Member

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    LOL! I think I'm going back to WTF -- short, understandable, and descriptive. ;)
  19. Mya Symons

    Mya Symons Mya Symons

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    I am in the middle of listening to the questions asked by reporters. Does it seem like they are saying the virus can not only be passed from person to person but also there are strains that could be passed from mouse to person?

    Does anyone know if they were having a rodent problem at incline village during that outbreak?
  20. Mark

    Mark Acting CEO

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    Some fragments of transcription:

    Dr Alter:
    "We think, basically, it confirms the findings of the Whittemore-Peterson Group."

    "It does, at least, confirm the findings of Whittemore-Peterson...I think one wants to go back to their studies because they've had more time, and they've done extensive work...so their study is more advanced than ours, but -with that as...er...with them having done the groundwork I think our study is highly confirmatory of their work..."

    Dr Lo:
    "Our findings show that the more diverse group of virus there is compatible with the XMRV, the xenotropic one, but really not identical and more closely related to the polytropic group."

    Q:
    "Does the finding of a polytropic virus suggest a looser association with CFS than finding a xenotropic would have?...It would seem to suggest more of a process of chance than a firm association."

    Dr Lo:
    "No, actually this group of virus we call the polytropic MLV - this is actually more characteristic of a retroviral infection...in fact what we found is it actually gives us a very good confidence this can not be an arbitrary artefact from PCR or contamination because the sequences are so varied from one patient to another."

    "They are in the same family but...they are compatible with the earlier finding of the XMRV, however they are not identical and they are more diverse."

    Q:
    And so is it usual that you would find an association with a single disease with this kind of a variety of viruses?

    Lo:
    "Yes, indeed, that's exactly what we anticipate for retrovirus infection...over time you will see the many different sequences there."

    Alter:
    "...The retroviruses...exist in big families of viruses...Hepatitis C is a very good example, nobody's infected with one variant... they have a whole huge family of variants...and if you take any given patient the patient will have multiple variants in them, and different patients will have different variants, so it's very characteristic of these kind of RNA viruses."

    "Since the original publication the WPI and NCI groups have found that they too are finding greater variability in their patients so it is not just XMRV as in the original cohort of patients."

    Lo:
    "I think...we can say we found this kind of variability that's actually MORE consistent with the natural form of a retrovirus infection in this group of patients."

    Alter:
    (regarding the discrepancies between different groups):
    "We think it's in the patient populations rather than the laboratory testing although the latter hasn't been completely ruled out...CFS is a syndrome, that's what it is, it's not a specific biopsy-proven diagnosis, and therefore it's subject to variability..."

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