Blood Products Advisory Committee Meeting Announcement (BPAC) December 14-15, 2010

[Bob]

Well, I guess it's not that easy, like Esther already said. If it was easy we would already have a cure...

I suppose we're not just at the 'limits of detection', but also at the limits of science/virology...
I never imagined it would be this difficult to nail down XMRV.

 

[Cort]

Ruscetti - has moved on and is working with animals and XMRV.

NCI-Fred has moved to generating animal models. Has purified XMRV virions, extremely pure. Cross-reactivity to native XMRV virions. (macaque infected models)
Will use them until pedigreed pos is agreed upon.

Chair question about WPI samples: SAIC said If came from WPI, had been tested by NAT.
Any different kind of antibody from those? No.

Nancy - serum or plasma? Answer - mixed.
XMRV is cloned, but also had MLV reagants from before that were used for MLVs - the MLV reagants worked reasonably well.
Nancy - an important point about the ROC curves, .62, seems pretty good. Judy is nodding. (Wish I understood.)

 

[Jemal]

They could still, very easily, decide to defer (not just discourage) diagnosed CFS donors at ALL blood banks on the precautionary principle until more is known. Why they haven't done that already is kind of a mystery to me.

I am at a loss also why they haven't taken this precautionary step. Maybe because they are scientists, they want hard evidence, before they make a move?

Or worst case scenario: deferring ME/CFS patients might give more credibility to the fact this is a real disease, potentially giving patients more leverage to get social benefits and stuff? I really am afraid reasons like this play a role here in the Netherlands...
(especially when the government is involved and not just objective scientists)

I suppose we're not just at the limits of detection, but also at the limits of science...
I never imagined it would be this difficult to nail down XMRV.

Yeah, I was also wondering if we are at the limits of science. It does look like this virus could open a whole new path to explore and might even explain several diseases, the cause of which is currently unknown.

 

[Cloud]

This virus violates some assumptions that are very convenient for researchers. The alternative looks so difficult it is frightening. Nature does not have to play by rules set by researchers. We are seeing the beginning of a paradigm shift.

put my thoughts into words...

 

[Cloud]

Coffin wants to see that virus isolated. (So do we!!). She might be saying that she can see variations in the viruses, again, which is good. Actually I don't think the answer to that question is reported....too b ad...



At the limits of detection! Yes...Some PCR's can pick it up and some can't. Could it be all about newer vs older machines? Or better vs not quite as good machines? Could it all come down to something like that? It starts to make a bit of sense given the inability to explain the disparate results, though....At the limits of detection.....Clever of her to try two different PCR machines



Interesting. As many patients with whatever she found (not classic XMRV - poly MLV's) recovered as remained ill - so if what she found is what the WPI found or related to it - you don't necessarily need to take anti-retrovirals to recover....if all this holds up.

My sense is that this is true....of course we need to define "recover"

 

[free at last]

Coffin wants to see that virus isolated. (So do we!!). She might be saying that she can see variations in the viruses, again, which is good. Actually I don't think the answer to that question is reported....too b ad...



At the limits of detection! Yes...Some PCR's can pick it up and some can't. Could it be all about newer vs older machines? Or better vs not quite as good machines? Could it all come down to something like that? It starts to make a bit of sense given the inability to explain the disparate results, though....At the limits of detection.....Clever of her to try two different PCR machines



Interesting. As many patients with whatever she found (not classic XMRV - poly MLV's) recovered as remained ill - so if what she found is what the WPI found or related to it - you don't necessarily need to take anti-retrovirals to recover....if all this holds up.

Just reading all this now Cort, hope the important points will be explained in laymens terms as we get to digest the information more.
That last sentence could be me right there Cort, for those that have followed my input and illness progression over 16 years.Though of course for xmrv not the polytropic variant.It seems encouraging to be reading this, as ive never fully got ( or seemed unlikely ) how someone with a retro virus, can over a long period of time seem to recover. with a very slow gradual calming of symptoms that takes many many years to unfold. But here we seem to be seeing this is exactly what can happen with some patients. Would be interesting to know how the recovery of those patients manifested over time. treatments they took suppliments they took. nutrition they was getting sleep patterns. If they took enviromental change measures.Mold avoidence ( i did not ) possibly many other factors that i cant presently think about.Interesting how the detection rate doesnt change from severe to recovered. Though caution on the small sample size. It all fits nicely in that the illness hasnt gone away has the potentiall to re surface. but often of a much lower strength of symptoms.and faster recovery times. I cant help but feel slighty in tune here Cort. Is it really this simple. Still reading here, but that last sentence posted really caught my eye. Those that have followed my story will know im not a mind reader i cant make my story fit evidence that is only just now surfacing. If the retro viruses play a part in causation of illness. clearly the body can in some situations, control or adapt , in some, as yet unknown way. wow. feels like vindication

 

[Dr. Yes]

All the posts and tweets cited here are by the valiant ValB626, whose complete postings from the meeting can be found here:

http://www.mecfsforums.com/index.php/topic,3875.30.html

She found some contamination in her controls - which in a weird way is good because it means she can find it (at least in part) if its there. She's doing culturing aka WPI but is considering moving to Lo's methods which are more sensitive which also makes sense - because as Dr Bateman pointed out the tests get better over time....so why use the best?

No, she did NOT say she found contamination in her controls!! Val's post is referring to the fact that Hanson used controls to CHECK for contamination via an assay for mouse mitochonrdial DNA. She also did NOT mention anything to do with culture methods at all. As for the different method she is talking about -- she said she is considering switching to Lo's assay for mitochondrial DNA from the one she is currently using (Switzer's?).

She is not finding XMRV.......She can tell because there is a specific deletion in the gag protein in XMRV that is not found in pMLV's and she's looking right at that area and its not showing up....

Her percentages are very close to the WPI - but she really is finding a different virus....

As Hanson stated before, and has been posted on this forum back when her abstract was first released, she does not want to say she has not found XMRV because she thinks the virus has yet to be accurately defined genetically speaking... hence her use of the term "classic" XMRV - which has the characteristic gag leader sequence deletion - to distinguish some strains from the "P-type" ones, which may come to be known as another form of XMRV (but which Stoye doesn't want to call XMRV at all). That's why Mikovits has been promoting the term HMRV which unifies the closely related X-type and P-type gag sequences. There appears to be a philosophical divide on this issue that, not surprisingly, pits the authors of the negative studies against those of the positive studies.

It is interesting to observe the rift at the meeting, with Lo/Alter/Hanson/Mikovits/Ruscetti on one side and Coffin/Stoye on the other. Coffin and Stoye, to my mind, are amazingly obstinate about the contamination issue, and ignoring all the obvious arguments against it (some of which were made by Lo and Alter in this meeting). Coffin's "nightmare" scenario is silly for a number of reasons, including that the WPI, NCI (which have found the same poly variants as Lo did) and Cornell labs would all have to have gotten that same contaminated bottle from similarly infected mystery mice in order for it to explain their findings. Anyway, the serology results on samples shared by Hanson with the NIH and WPI independently - which apparently correlate with Hanson's PCR results - make it even HARDER to believe any contamination scenario. (Antibody reactivity itself is, of course, a very strong argument against contamination, but notably the more evidence piles up supporting the positive findings, the further the skeptics have moved the goalposts; Stoye's increasingly ludicrous demands go far beyond anything that was expected of his own, or anyone else's, past studies on MLV's. By his newly espoused logic, most of the MLV study findings done for the past two decades would have to be re-examined...

That's all I can post about this (or should).. now off to bed to let my immune system allegedly fight the alleged retrovirus that was allegedly found in my blood (that's where 'balance' gets you... :Retro wink

 

[Cort]

Originally Posted by Cort
She found some contamination in her controls - which in a weird way is good because it means she can find it (at least in part) if its there. She's doing culturing aka WPI but is considering moving to Lo's methods which are more sensitive which also makes sense - because as Dr Bateman pointed out the tests get better over time....so why use the best?

No, she did NOT say she found contamination in her controls!! Val's post is referring to the fact that Hanson used controls to CHECK for contamination via an assay for mouse mitochonrdial DNA. She also did NOT mention anything to do with culture methods at all. As for the different method she is talking about -- she said she is considering switching to Lo's assay for mitochondrial DNA from the one she is currently using (Switzer's?).

My apologies and thanks for clearing it up. (the post said mtDNA contamination -controls and didn't mention the ME/CFS patients. I assumed too much. Thanks for the other fix.

It'll be great to get a resolution to all this at some point.

ValB626 did a superb job - I was amazed she was able to get all that out.

 

[Cort]

Just reading all this now Cort, hope the important points will be explained in laymens terms as we get to digest the information more.
That last sentence could be me right there Cort, for those that have followed my input and illness progression over 16 years.Though of course for xmrv not the polytropic variant.It seems encouraging to be reading this, as ive never fully got ( or seemed unlikely ) how someone with a retro virus, can over a long period of time seem to recover. with a very slow gradual calming of symptoms that takes many many years to unfold. But here we seem to be seeing this is exactly what can happen with some patients. Would be interesting to know how the recovery of those patients manifested over time. treatments they took suppliments they took. nutrition they was getting sleep patterns. If they took enviromental change measures.Mold avoidence ( i did not ) possibly many other factors that i cant presently think about.Interesting how the detection rate doesnt change from severe to recovered. Though caution on the small sample size. It all fits nicely in that the illness hasnt gone away has the potentiall to re surface. but often of a much lower strength of symptoms.and faster recovery times. I cant help but feel slighty in tune here Cort. Is it really this simple. Still reading here, but that last sentence posted really caught my eye. Those that have followed my story will know im not a mind reader i cant make my story fit evidence that is only just now surfacing. If the retro viruses play a part in causation of illness. clearly the body can in some situations, control or adapt , in some, as yet unknown way. wow. feels like vindication

Just learning about those 'recovered' patients would be fascinating in itself...how recovered were they? What did they do that helped them get better? Are there any commonalities? What about the unrecovered patients? Were they different to start off from those that got better.

It would be easy to develop a survey and ask them........

Another thing that you wonder - why is this not being done?

 

[Cort]

As Hanson stated before, and has been posted on this forum back when her abstract was first released, she does not want to say she has not found XMRV because she thinks the virus has yet to be accurately defined genetically speaking... hence her use of the term "classic" XMRV - which has the characteristic gag leader sequence deletion - to distinguish some strains from the "P-type" ones, which may come to be known as another form of XMRV

We shall see - and this is what I thought until I had a talk with a retrovirologist (out shortly). He said Alter's sequences were very close to endogenous retroviruses and not nearly as close to XMRV. He felt that if they were part of a swarm, so to speak, of XMRV-like retroviruses then then they would have swarmed around XMRV -been more similar to them - instead of looking like the other endogenous retroviruses....He didn't think this was determinative and Lo/Alter, from all appearances seemed very confident.

I think they know what pMLV's look like - my guess is that they've been studied for quite awhile. The way it could all fit is if they sequence out the rest of the virus and find bits of XMRV like materials in there. He said something like that would convince him. Or if they isolated the virus - if they did that I imagine Stoye and Coffin would stop right there.....Or if they found in integrated into human DNA - there are a couple of steps that, if they could accomplish them - alot of these questions would drop away, I imagine.

To be completely honest, I flip like the wind with XMRV - someone says one thing - I think about it and think "oh shit!" and then someone says another thing and I think 'Great!" -we've got it.

Its amazing what a mess it is! Unless I missed something it looks like months more work (???). Hopefully we'll get more clarity about the meeting in the webinar.

 

[Cort]

The truth will out over the next year! . Oh boy (a year) - but it certainly will.

And some VERY STRONG points. Reproducible over time - Dr. Alter's ability to find the virus again in those eight patients really looms very large. How do you do that if its not a virus?

Get the right assays - and you'll get the results

In those labs who do find the agent, it's very reproducible. Year after year, same paitents.

Confirmed by sequencing, reproducible over time.

He is a LASKER Award winner - the top of the heap so to speak......a good man to have in your corner....

He's a little tired of Stoye

Stoye used single-case anecdotal info to try to make a case.

A strong confident statement from Lasker...:victory::victory:

If it's NOT XMRV, we must continue the research to find out what is.

And, of course, this is so encouraging. We have a Nobel Prize for Medicine winner (Lasker) in our corner. Actually we have two of them Dr. Houghton??? on the CFSAC panel is another- two individuals who, like many others, after having got to know people with ME/CFS - have gotten hooked; they believe its real, they know its serious and they want it to get more funding. Dr. Lipkin is assuredly another one - these people are powerful people in their field....It can only help.

Dr. Alter:

when a group finds a new agent, become biased it's real. When it's not found by another group, they become even more biased it's unreal.

Our goal should be to find the truth. The truth wlil out over the next year. I concur we have no evidence for causality, esp when we're at the LoD and assay perf is so critical.

But I still want to counter by saying that the current evidence for disease association is very strong that XMRV or MLV is strongly associated with CFS.

In those labs who do find the agent, it's very reproducible. Year after year, same paitents.

Confirmed by sequencing, reproducible over time.

Dr. Hanson has demonstrated how criticalthe assays are. When tweaked assays, findings identical to Lo lab.

Diversity of XMRV/MLV being confirmed in WPI lab, so not only agent being confirmed there.

In 100s of neg controls in same lab, extremely neg, has done what Coffin recommended was also neg. Always neg for contam. It isn't logical to suggest otherwise.

Stoye used single-case anecdotal info to try to make a case. Simply because it has happened in the past isn't valid to negate reproducible data from 4 diff laboratories.

I'm not a CFS Dr, but have learned alot in last 6 months. Absolutly convinced when you define this by proper criteria, it's a very serious, medical disease. Chars of a viral disease. If it's NOT XMRV, we must continue the research to find out what is.

 

[free at last]

Yes, I don't think XMRV is causing fatigue that quickly. Also most animals need to be really sick, before they display it openly. They don't want to show weakness, because of possible predators.

Agreed Jemal i dont think xmrv is causing fatigue that quickly either.infact if i may be allowed to guess my infection time 13 years ( i have reasons for possibly believing or knowing my infection time, ill elaborate if anyones interested ) 13 years i may have carried this virus before illness started and a diagnosis of CFS/ME. on reflection i agree a series of immune insults and a general weakening of the immune system for 13 years led to what finally happened CFS.

In my case ( there will be many others for lots of different people ) for me habitual pot use, which has been shown to lower the immune response. But for others we could be talking alcohol, stress, mental illnesses ( affecting the immune system ) and enviromental issues, chemicals ( both in food and the enviroment. Mold exposure ect. and on and on.It seems the triggers could infact be different for different people. which is why i stated no one theory should fit right at the top of the tree for a suspect trigger, that its all relevent.And that what is a trigger for one may not nesseceraly be a trigger for another. explaining those differences between say my experiance, and Lisas ( and freinds )

The monkeys really should have been smokking pot drinking to excess, got very stressed with there job at the zoo. lived in a cage with mold. ( around the chemical factorys of Texas ) caught EBV Toxoplasmosis. Influenza chicken pox.and many other nastys over a period of say 13 years from xmrv ( or polytropic infection ) to really see the deal with these new retro viruses. of course these studys are way too incomplete.Agreed Jemal. My comments about the monkeys please take lightly i dont mean any of that at all. i just want to prove a point that these puzzles may be unfolding right before our eyes. I want nothing but humane treatment for them, during these tests. Difficult to do humanely agreed. and is seperate discussion of itself.But in no way approve of mistreatment for them

 

[urbantravels]

Dr. Alter:

when a group finds a new agent, become biased it's real. When it's not found by another group, they become even more biased it's unreal.

Our goal should be to find the truth. The truth wlil out over the next year. I concur we have no evidence for causality, esp when we're at the LoD and assay perf is so critical.

But I still want to counter by saying that the current evidence for disease association is very strong that XMRV or MLV is strongly associated with CFS.

In those labs who do find the agent, it's very reproducible. Year after year, same paitents.

Confirmed by sequencing, reproducible over time.

Dr. Hanson has demonstrated how criticalthe assays are. When tweaked assays, findings identical to Lo lab.

Diversity of XMRV/MLV being confirmed in WPI lab, so not only agent being confirmed there.

In 100s of neg controls in same lab, extremely neg, has done what Coffin recommended was also neg. Always neg for contam. It isn't logical to suggest otherwise.

Stoye used single-case anecdotal info to try to make a case. Simply because it has happened in the past isn't valid to negate reproducible data from 4 diff laboratories.

I'm not a CFS Dr, but have learned alot in last 6 months. Absolutly convinced when you define this by proper criteria, it's a very serious, medical disease. Chars of a viral disease. If it's NOT XMRV, we must continue the research to find out what is. .

Sounds like Dr. Alter really came down from the mountain on this one.

GO DR. ALTER!!!

I only wish there had been tape rolling on that.

 

[Cort]

Sounds like Dr. Alter really came down from the mountain on this one.

GO DR. ALTER!!!

I only wish there had been tape rolling on that.

I agree. He really got rolling on that one.....The man is engaged...

 

[Cort]

Stoye is really playing hardball! He sounds a bit tweaked. I wonder what he was like on tape??

Member - doesn't know about XMRV, but listening to all the other viruses and co-infections, makes sense to me to permanently defer them. Why does FDA think educational materials is worthwhile.

Audience member - early days of AIDS or whatever it was called back then. Asked potential donors if they had a risk factor for HIV to self-defer. Data show it was very effective.

FDA guy - Hard to diagnose, have a way to differentiate disabling fatigue from being tired today. Would need much insight from clinicians.

Stoye - UK deferred CFS pts on the basis of their own health. This decision was met by derision, had nothing to do with pt health.

FDA - No country is asking a specific donor question now. It would indicate a higher level of certainty than yet warranted.

Flemish Red Cross actually does ask the question. Self-defer about same rates, so not additionally effective, apparently.

Its interesting that no countries except the Belgians are actually asking anyone directly if they have CFS!

 

[Cort]

Finally they get to the cancer part.....They certainly acknowledge the potential for damage....For the first time we hear that Dr. Klimas sees mantle cell lymphoma patients in her practice...(wow). (When is the Peterson Cancer paper going to get published? ...it's been a year and a half since they reported that at the conference)

Coffin says when we get a good assay, if its in the population - then test for it even if we aren't sure what diseases its causes - ITS TOO SCARY

Chair - There have been studies where pts were looked at 20-25 years later. Longitudinal data in Germany, too. (Not CFS pts).

Ray - What's troubling the FDA. Studies will tell us in the next year or two of transmission. Proof of causation will alot longer. These viruses are in a bad family when you look at what they affect. Neuro-immune, cancers, etc. Should we wait??? With another (foamy?) virus, were in similar situation with conflicting studies. But no disease association anywhere.

Nancy - Mantle cell lymphomas in Peterson's CFS patients. Nancy sees EBV-related lymphomas in her practice. I'm afraid of oncogenic potential w/these viruses.

Coffin - If accept it's present in some ppl, have a good assay, and it's being transmitted by blood transfusion, I'd consider it highly prudent to test, even if we don't have proof of causation in disease. Too many other htings it could be doing that are bad.

Judy - 30% of Dan Peterson's cohot with either CLL or mantle cell. Have samples where can isolate the virus going back to 1984. A number of cases who have gone on to develop mantle cell.

I think that's it - Val did an amazing job!

 

[sensing progress]

Cort, where does that Dr. Alter quote come from? (sorry if you already mentioned it)

 

[Cort]

http://www.mecfsforums.com/index.php/topic,3875.120.html

Do you want to frame it?

I feel so much more confident when these guys get engaged. They are the kind of people we've been looking for for decades....

 

[Rivotril]

leGrice said some months ago the contamination issue would be ruled out (or not) in next couple of weeks.
after all these waiting, we got nothing. still stoye/coffin versus judy and alter about comtamination yes or no...nothing has changed since the xmrv workshop, same discrepancies still exist, cant believe it...

They didnt do what le grice promised (solve contamination issue)
they keep repeating same arguments
wasting valuable time with doing nothing

why only a blood ban if causation is proved? never heard something as stupid as that.

a disappointment again after workshop...

only positive thing was to hear dr alter saying the things that were mentioned in the posts above...i'm glad that he is in our "camp".

for the rest it was crap, all about politics, egos and money.

like jemal said: they just dont want bloodban because it gives a signal that ME/CFS is not between the ears, so that sick ME/CFS patients have some stick to whip the insurance companies/disablity payment things with..

just wait another year for lipkin...and then again WPI finds things and CDC wont, and so we go on.....
hope that judy and dr alter will go fighting for us, and eventually the truth will come out, but with all this downplaying and slowdowning the process it will take ages

 

[VillageLife]

Alter - Rocks !!!!!!!!!!!