Article: The Singh XMRV Study Strikes Out

You can view the page at http://forums.phoenixrising.me/content.php?418-Singh-XMRV-CFS-Study-Strikes-Out

 

i thought jolicoeur didnt find it. and i asked the alberta researcher..he said we are "still trying" to find it.

 

I really, really hope the WPI has done fully blinded re-tests using freshly collected samples from patients and most importantly healthy controls. I also hope they would be willing or able to admit they are wrong if they discover they made a mistake. They are at or past the point where they can admit they are wrong or that it is was a lab contaminate without looking incompetent. I know these statements will spark emotions here but Dr. Mikovits needs to take the contamination possibility seriously for her own reputation sake and address the problems other has risen with her data in a calm cool collected manor presenting science to back it up. The WPI has jumped from one explanation to another for why others are not finding it, enough with the excuses, there are better ways to handle this then just blaming and attacking everyone who can not find it. Enough is enough, this is damaging to the reputation of CFS to those we need the most at this point, researchers and doctors. I see scientist blogs discussing CFS and XMRV like Professor Racaniello filled with comments from CFS patients attacking anyone and everything that disagrees that XMRV is present in CFS patients. This is helping no one and closing doors we need to keep open.

 

Thanks Cort as always for putting us in the picture - even if a bit of a cliffhanger. I think we await the London May conference Iime with much anticipation as to which Viruses exactly they are finding (and treating) in the Gut.

 

Thanks for this, Cort. It's not looking good for XMRV at the moment and I think LJS is right - as patients we need to try to maintain a good relationship with scientists who are acting in good faith in trying to get to the cause of our disease and yet don't get the results that many of us hoped for. We mustn't flame people down as has so often happened in the past. If XMRV really does go down the pan we need to keep scientists on board to investigate other possible causes.

We've got a lot of exposure, thanks to XMRV - scientists are aware of how many of us are so very sick and have seen there's an important puzzle to solve. Let's not drive them away.

 

Thanks, Cort.

One issue that concerns me is the detection of 'XMRV' antibodies in other studies and the suggestion that these are down to cross-reactivity with related but non-XMRV viruses, probably retroviruses.

They also noted, however, that serological (ie antibody) results are not nearly as susceptible to contamination but are susceptible to false positives if they cross-react to other pathogens or other proteins.

But what would these virsues be? I thought human retroviruses were incredibly rare, or is it just diseases-causing retroviruses that are believed to be rare. If there were XMRV-like viruses out there, that would surely be just as big a story?

As for contamination and explaining the difference in WPI positive rates for patients vs controls, one possibility did occur to me, though I may have got this wrong: I seem to remember Judy Mikovits saying they often had to test samples several times to get a positive results (please tell me if I got this wrong). Were controls retested too i.e. if a control was negative was it reteseted? If not, patients would automatically have more chance of positives. Secondly, if a patients tested positive, was this retested to confirm it or did they stop at that point? If, as Singh found, there were a low level of false positives, if you retested the negatives you'd get more positives, retest those negatives remaining to get more positives and so on unitl you ended up with a high level of positives for patients. But maybe WPI retested all their patient positives to confirm the results.

Finally, I agree it's important we keep good scientists on board. Singh, Alter and Coffin have all said that CFS is an important disease that needs to be taken seriously with more research, and that a viral explanation looks very likely - even it's not XMRV. To me, this looks like a breakthrough: top-notch scientists with access to serious research money taking an interest in our neglected disease.

 

Not the results I was hoping for or expecting (I misinterpreted the significance of Dr. Singh's patent applications), but thank you, Cort, for your thorough report.

What a puzzle, what a disease. All we can do is press for more research.

 

"The most problematic finding for XMRV is not that researchers are finding it but declaring it to be a contaminant (although that has happened in three published studies and one unpublished one) but that once again, they are simply unable to find evidence of the virus even in low levels in CFS patients and other disorders. At this point the question where it came from - the product of a laboratory accident or an escape from mice - is somewhat irrelevant. Researchers have to find the virus in people with ME/CFS before they can associate it with the disease"

The most problematic finding for XMRV is not that researchers are finding it but declaring it to be a contaminant

I agree with this statement Cort. Coffin found XMRV, and claims it is contamination in an unpublished study. BUt he has yet to prove where the contamination came from in an unpublished study. SO the WPI, the FDA, and Coffin found XMRV. Just Coffin claims there is contamination and wants to forget all about it.

 

Anything but XMRV?

I'm generally agnostic about XMRV to date and don't usually subscribe to conspiracy theories but there is a recent pattern, dare I say meme developing whereby researchers and commentators who do not believe the XMRV association tend to repeat three statements almost identically :

(a) we now recognise the suffering of ME/CFs patients and believe that ME/CFS is a very real and disabling disease;

(b) that its is very likely that ME/CFS is caused by some sort of virus and we should continue to search for it - it just isn't XMRV;

(c) ME/CFS patients should in no circumstances take ARV's.

The first statement could be genuine concern where researchers have come into contact with ME/CFS patients for the first time (like Alter) but similar statements have also been made by commentators not involved in ME/CFS research. Perhaps its merely a sop to patients to 'let us down gently' after all the optimism?

The second statement, while welcome doesn't appear to be directly linked to any particular evidence and in the UK at least is at odds with the current mainstream medical opinion that determines that the etiology is unknown but recommends psychological treatments. Perhaps another sop to patients who want to 'believe' that their illness is viral? What is remarkable is that it appears to be completely uncontroversial to suggest that the culprit may be EBV; HHV6, various enteroviruses or even Huber's HERVs. But XMRV - no way!

The last statement is bizarre and its appearance in more than one research paper even more so.

Surely any level headed commentator must realise that any treatment with ARV's is likely in only a handful of cases and the need to continually make this point in print is completely out of proportion. The majority of patients in Europe wouldn't be able to access ARVs even if they wanted to. What motivates this statement? Concern for patients when one of the three leading causes of death is suicide? ARV drug resistance has been mentioned more than once but represents a vanishingly small risk compared to non-compliance with treatment of hundreds of thousands of HIV patients? The potential for facing the uncomfortable possibility of patients being cured?

Beats me what this meme is all about.

 

(b) that its is very likely that ME/CFS is caused by some sort of virus and we should continue to search for it - it just isn't XMRV;
...
The second statement, while welcome doesn't appear to be directly linked to any particular evidence and in the UK at least is at odds with the current mainstream medical opinion that determines that the etiology is unknown but recommends psychological treatments.

Hard to see why virologists/emminent scientists who aren't part of the UK establishment saying CFS looks viral is a bad thing - as you say it challenges mainstream opinion head on.

 

Thanks, Cort.

One issue that concerns me is the detection of 'XMRV' antibodies in other studies and the suggestion that these are down to cross-reactivity with related but non-XMRV viruses, probably retroviruses. But what would these virsues be? I thought human retroviruses were incredibly rare, or is it just diseases-causing retroviruses that are believed to be rare. If there were XMRV-like viruses out there, that would surely be just as big a story?

As for contamination and explaining the difference in WPI positive rates for patients vs controls, one possibility did occur to me, though I may have got this wrong: I seem to remember Judy Mikovits saying they often had to test samples several times to get a positive results (please tell me if I got this wrong). Were controls retested too i.e. if a control was negative was it reteseted? If not, patients would automatically have more chance of positives. Secondly, if a patients tested positive, was this retested to confirm it or did they stop at that point? If, as Singh found, there were a low level of false positives, if you retested the negatives you'd get more positives, retest those negatives remaining to get more positives and so on unitl you ended up with a high level of positives for patients. But maybe WPI retested all their patient positives to confirm the results.

Finally, I agree it's important we keep good scientists on board. Singh, Alter and Coffin have all said that CFS is an important disease that needs to be taken seriously with more research, and that a viral explanation looks very likely - even it's not XMRV. To me, this looks like a breakthrough: top-notch scientists with access to serious research money taking an interest in our neglected disease.

I asked Satterfield about the cross-reactivity. He did not believe it was to other MLV viruses or retroviruses - he said it could easily be to a common virus.

Yes, Dr. Mikovits said they did retest some samples several times. Some samples were also positive on the first go around. My impression was that they didn't retest the control samples if they were negative - so retesting the CFS samples could boost the positive rates.

 

I asked Satterfield about the cross-reactivity. He did not believe it was to other MLV viruses or retroviruses - he said it could easily be to a common virus.

Yes, Dr. Mikovits said they did retest some samples several times. Some samples were also positive on the first go around. My impression was that they didn't retest the control samples if they were negative - so retesting the CFS samples could boost the positive rates.

Hey Cort,

Is Satterfield the best source to be counseling about cross-reactivity if he's never been able to find XMRV in a single patient?

 

I think you're mixing apples and oranges. Whether or not someone has been able to find XMRV or not doesn't have anything I can think of to do with their knowledge of cross-reactivity?

Satterfield is one of the few professionals in the field that is willing to talk about these issues. He's not necessarily special but he is someone who makes his living running a diagnostic lab - so I think his opinion, given that we have so few from the professional arena, is worth listening to.

(Right now with 26 studies unable to find XMRV he's actually in the majority....)

 

As for contamination and explaining the difference in WPI positive rates for patients vs controls, one possibility did occur to me, though I may have got this wrong: I seem to remember Judy Mikovits saying they often had to test samples several times to get a positive results (please tell me if I got this wrong). Were controls retested too i.e. if a control was negative was it reteseted? If not, patients would automatically have more chance of positives. Secondly, if a patients tested positive, was this retested to confirm it or did they stop at that point? If, as Singh found, there were a low level of false positives, if you retested the negatives you'd get more positives, retest those negatives remaining to get more positives and so on unitl you ended up with a high level of positives for patients. But maybe WPI retested all their patient positives to confirm the results.

Yes, Mikovits did say something like that, about a year ago. I think you are right-on with this hypothesis, if that is how they repeat tested to get their positives. But there might be other explanations, if past failed retroviral searches are a model for this situation.

 

(c) ME/CFS patients should in no circumstances take ARV's.

...

The last statement is bizarre and its appearance in more than one research paper even more so.

Surely any level headed commentator must realise that any treatment with ARV's is likely in only a handful of cases and the need to continually make this point in print is completely out of proportion. The majority of patients in Europe wouldn't be able to access ARVs even if they wanted to. What motivates this statement? Concern for patients when one of the three leading causes of death is suicide? ARV drug resistance has been mentioned more than once but represents a vanishingly small risk compared to non-compliance with treatment of hundreds of thousands of HIV patients? The potential for facing the uncomfortable possibility of patients being cured?

Beats me what this meme is all about.

If you study the side-effects of ARV therapy this concern makes perfect sense. Some ARVs have side effects that likely would worsen CFS symptoms, and one in particular, AZT, is totally contra-indicated. That is because AZT is toxic to the bone marrow. Well, CFS involves low blood volume, if we are to ever have a chance of re-growing our missing blood volume we definitely will need healthy bones and productive bone marrow (all blood cells are produced in the bone marrow).

There may be treatments that work but have terrible side effects, and some ARVs may fall in that category. I once had a doctor tell me he could kill all the pathogens in my body in about 1-2 hours, with a strong IV, but I would not survive either. That is what this meme is all about...

 

"Their two antibody tests did not reveal XMRV was present and they suggested this meant the positive results in the original study may have been due to a cross-reaction to another virus or protein and not to XMRV."

Does anyone know what viruses they are referring to? Would herpes viruses, for example, cross react to an XMRV antibody test or would it have to be another retrovirus in order to cross react? Is there any scientists or anyone else familiar with this who can answer this question? Please and thankyou.

 

I asked Satterfield about the cross-reactivity. He did not believe it was to other MLV viruses or retroviruses - he said it could easily be to a common virus.

I thought the whole point about antibodies is that they are pretty specific, so while they won't necessarily only detect one virus, other virsues they detect would have to be pretty close cousins. So an anti-XMRV antibody would presumably only react with, say, MLV-like viruses. That was the logic used in the original Lombardi paper which identified 'anti-XMRV' antibodies using techniques targeted not at XMRV but at its close cousins (e.g. they used one technique "which reacts with all polytropic and xenotropic MLVs"). So on the face of it, the 'any old virus could cross-react' line doesn't seem that likely.

 

"The Singh XMRV study strikes out." That's a good way to put it, they found nothing.

 

This has got to be a sock in the gut for the WPI after so many hopes were raised. If they aren't careful, they are going to get stuck in a self-perpetuating loop in this futile XMRV chase. It was a good try and an honest mistake, which actually began at the Cleveland Clinic, one of America's most conservative and respected research institutions. Refocusing on more generalized research now is in order.

 

Posted on VR's blog today:



"After the recent publication by Ila Singh on XMRV in CFS patients, Dr. Lipkin sent me the following note:


Dear Vince-

We have a plethora of explanations for how CFS/XMRV/MLV studies could go awry. However, we dont have evidence that they have. Absent an appropriately powered study representing blinded analyses by Mikovitz and Lo/Alter of samples from well characterized subjects using their reagents, protocols and people, all we have is more confusion.

I remain agnostic. We wont have answers until the end of 2011.

The NIH will post something on our study today.

Ian"


http://www.virology.ws/2011/05/06/i...m_campaign=Feed:+VirologyBlog+(virology+blog)