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

[urbantravels]

Well, we'll hear more about that in the Friday webinar.

 

[urbantravels]

According to Amy Dockser Marcus the recommendation *is* for a screening question to be added, not just to defer patients who volunteer the information:

http://online.wsj.com/article/SB10001424052748704694004576020321854485688.html

An advisory committee to the federal Food and Drug Administration is recommending that people with chronic fatigue syndrome be barred from donating blood, amid concerns a retrovirus may be linked to the disease.

The panel voted Tuesday 9 to 4 that the FDA should require a screening question to ask potential donors if they have a medical history of chronic fatigue syndrome and, if so, exclude them from donating.

The recommendation by the panel must now be reviewed by the FDA, which typically follows the advice of such panels but is not required to do so. An FDA spokeswoman said there was no timetable yet on a final decision.

 

[RivkaRivka]

it took a long year since the Science paper, but this FDA committee did the right thing! this is a victory for all people will need blood tranfusions in the US (5 million per year) and also a victory for just the reason dr. mikovits stated in the WSJ article.

from the article:

"Judy Mikovits, who led the team of researchers that published the study in Science linking XMRV to chronic fatigue syndrome, said Tuesday's decision is a victory for patients because "for the first time ever, they are being seen as sick with an infectious disease.''"

 

[gracenote]

I don't know if someone already addressed this - but I think the "recovered" patients of Dr Bell that are being studied by Hanson may have been discussed in an article this summer by Bell and Bell. (viral results appear about the same in current and "recovered" patients)

My general memory (with the usual disclaimers of faultiness) is that the Bells found that CFS patients whose orthostatic intolerance improved or disappeared, considered themselves "recovered", but when looked at more closely, they were still having lots of other symptoms. So the OI accounted for much of the disability in functioning, but even when the OI and functionality improved there were still symptoms of illness.

I can't locate the article just now. I think the Bell and Bell article may have been in some online publication from a UK ME group, and you had to page through the very lengthy publication to read the Bell article - couldn't just clip and post it. Maybe someone with a better memory or google-ability can locate this.

Here it is. It is part of the Invest In ME Journal. You'll need to scroll down to page 23 for the full article.

Definition of Recovery in Chronic Fatigue Syndrome

Author: David S. Bell

Year: 2010

Published In: Journal of IiME

Full Text Available:

http://www.investinme.org/Documents/Journals/Journal%20of%20IiME%20Vol%204%20Issue%201.pdf

Abstract

The definition of clinical recovery as long been debated in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). Clinically, many persons who have had ME/CFS declare themselves recovered or nearly recovered while continuing to present for medical care because of ongoing somatic symptoms. In this study ten persons who considered themselves recovered or nearly recovered were given questionnaires to assess health status and compared to healthy adults.

Half of the recovered subjects would be considered ill with CFS based upon the disability requirements of the CDC empiric definition of CFS, and all recovered subjects had significant somatic symptoms. Yet these subjects had all returned to normal in the symptom of orthostatic intolerance so that their daily activity was normal.

Thus the perception of recovery in ME/CFS is related to the ability to sustain upright activity and not related to the degree of somatic symptoms, including fatigue.

 

[Valb626]

Pretty darned good translations of my short-hand and garbled notes, Cort.

I went back over them and tried to fix some of the typos and clarify some of the points.

A few things:

Hand-outs of the slides from a few of the presentations were available before the meeting started, which is why Heidi and I were posting about results before the presentations happened...lol

WB is whole blood

Villinger's point about monkeys with AIDS is that until end-stage, it's hard to observe much change in behavior because they all go nuts when humans are around, so if the XMRV-pos monkeys were sleeping more or had lower activity levels, they'd be unlikely to observe it. They'd have to set up behavior-monitoring equipment to look for increased sleeping, lower activity level, etc. and that isn't what they were/are doing.

Yes, Bell and Bell collected survey data on the "severe," "recovered" and healthy patients. There were some graphs comparing symptom self-reports from the different groups. The recovered patients had a lot fewer symptoms than the severe patients, but they still reported more symptoms than the healthies (statistically sig difference on most of the measures).

And, Dr. Yes, thanks for clarifying that.

I actually felt it was a very good day for us. Stoye was really "reaching" in his presentation and Coffin was a one-point/trick pony with his repeated "show me the virus" questions. But their voices seem to be getting weaker... I think we're good. Just not quickly enough.

 

[Cort]

Fantastic Job ValB262 - I could hardly keep up with you....you have quick fingers...

Recovered hardly seems recovered - just quite a bit better. I wonder if there was anything in common with them or if they just slowly got better over time...

 

[Berthe]

I just think that happens all the time...but the way to shut these guys up is to isolate the virus or prove its integrated into human DNA or provide some other data that shuts them up. Alter/Lo have more work to do....in order to silence the naysayers. They are working on isolating the virus - hopefully they will do so soon.

Haven't we heard several times from Coffin and elsewhere that pMLV's are not infectious in humans? That is my recollection.

Didn't these guys read Ila Singhs articles?

 

[Deatheye]

Didn't these guys read Ila Singhs articles?

Was it Singh that showed the virus RNA integrated into human DNA? I thought there was a paper allready showing that.

 

[bertiedog]

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

Also they should have been injected with different forms of mercury in the way many of us were like thimerosol and also the form of mercury found in dental amalgams and then really stress their bodies not allowing them sufficient rest, sleep etc as tends to happen in our society today. Perhaps then they might have seen fatigued monkeys!

 

[Bob]

Arguments that mitochondrial DNA could not be involved violate considerable observation that mitochondrial disease is part of the syndrome. The implication that this is impossible gets back to arguments about low replication fidelity, which is being observed in reported data.

anciendaze, are you referring to a discussion about human mitochondrial DNA, in relation to XMRV, that occurred in this conference? If so, would you mind highlighting it please? I can't find it.

Arguments about the necessity of nuclear DNA must be tempered by those long forgotten observations of low ESRs in a subset of patients. This is due to misshapen erythrocytes. Mature (mammalian) erythrocytes do not have nucleii.

Would you mind expanding on what you are talking about here please? What are the arguments about the necessity of nuclear DNA, what are ESR's and how to erythrocytes fit in here? (Sorry, it's just that it sounds interesting, but you've lost me!)

Meanwhile, back in the real world, things are definitely happening. Research efforts are being started with whatever funding can be scraped together. Companies who pay attention to the bottom line are tweaking existing antiretrovirals for XMRV and MLVs. (Check on Chimerix.)

I did check on Chimerix, as you suggested, and I found this...
http://www.chimerix-inc.com/news-an...nstrates-positive-phase-1-clinical-results-w/

...results from a series of preclinical studies showed that CMX157 exhibited highly potent in vitro activity against human immunodeficiency virus (HIV), including HIV strains resistant to current therapies, potent in vitro activity against xenotropic murine leukemia virus-related virus (XMRV), a blood-borne retrovirus recently associated with chronic fatigue syndrome (CFS)...

(Interesting that a pharmaceutical should work so well on a contaminant/rumour virus!)

The fact that opposition tactics involve playing for time should be considered positive. Nothing that happened today shows it possible to stop this train.

I agree! The progress is disappointingly slow, but the evidence is always getting stronger.

 

[Bob]

Does anyone know if I am right in thinking that there was a discussion about Mouse mitochondrial DNA? Was there a discussion that pMLV's could be a contaminant from Mouse mitochondrial DNA and did Coffin suggest that it is difficult to check for mouse mitochondrial DNA contamination?

Here's the posts with the mitochondrial discussion:
http://forums.aboutmecfs.org/showth...ber-14-15-2010&p=143356&viewfull=1#post143356
http://forums.aboutmecfs.org/showth...ber-14-15-2010&p=143359&viewfull=1#post143359

It's very confusing and they seem to be discussing both mouse and human mitochondrial DNA, in the second post.

I don't understand too much about about mitochondrial DNA... maybe I should do a wikipedia search and have a read about it!

 

[Jemal]

from the article:

"Judy Mikovits, who led the team of researchers that published the study in Science linking XMRV to chronic fatigue syndrome, said Tuesday's decision is a victory for patients because "for the first time ever, they are being seen as sick with an infectious disease.''"

Not so sure if all the committee members share that opinion, most would insert a "possibly" into that last sentence I think

Anyway, in 2011 we will definitely get an answer. Or otherwise in 2012. Or maybe in 2013...

I guess I was hoping for a bit more.

 

[free at last]

Everybody feels the same im sure Jemal.

But maybe we are not focussing enough on what didnt happen, there are those that would probably have very much liked to prove that contamination was at the root of all this. And they havent been able to do that. Maybe these studys had the potential to kill all this stone dead, many must have been worried that was a possible outcome. I dont see that at all, surely this is good news in a retrospective kind of way.

In other words the games are still on, we didnt get it all our way.But from what i can see so far, neither did the likes of Mclure.

And from what i can see of what theyve actually done to clear all this up.It doesnt appear to me that they really have done a lot, or enough to unscamble this scientific mess, Hard as it may be.

I hope this was not intentional by them, because i know how i feel, and i think i sense the same dispair on many posts here. If that was a tactic being used here ( example small sample sizes being mentioned as one gripe ) then i for one will not let them get to me.We must sit back a bit, and digest the good and the bad, bounce back with all the brilliant minds on this forum that can pour over what good has been learned from what theyve allowed us to know, or have this time around.

For example the pcr machines giveing different results is something we never knew about, and must be a lenghty investigation of itself to figure how much this has affected results so far around the world ? Hansons study is also interesting both in confirmation of retroviral infection of CFS/ME patients, and the facts about detection rates still being high in those partially in recovery. Or symptom reduced stages of the illnesses. This really needs more work and understanding whats going on in those whose symptoms are over the years modifying in a more bearable way.

Is it a good thing ? short term i can tell you yes definately. Long term ? im not so certain, and indeed a little worried about cancer.There is things to be moving foward with here, please dont lose faith that our time will come. we have achieved so much thanks to the WPI, the game is not over yet by a long shot, is what im focussing on from these early revelations ( or lack of them )
Lets also from now on, not build ouselves up for revelations that are to painful to digest, when we dont get what we want or expected. Its self deafeating, and half of the problem. I have certainly been guilty of this, ( we all want hope you see ) but we are playing right into the hands of those that doubt us, when we self deflate ourselves through to high a expectation.

 

[pictureofhealth]

Didn't these guys read Ila Singhs articles?

Agree with you Berthe. Perhaps we should send out a copy of Ila Singh's XMRV findings to Stoye and Coffin.

Biggest take away for me from this - Alter is really engaged with this research now!

 

[Cort]

Good points Free At last - we actually did learn alot - we just didn't get the big revelation we hoped for and really did expect...

The PCR machine differences were really astonishing.

I thought Judy's statement about their long culture times vs the shorter culture times in other studies may be very instructive. (If the pathogen is so rare then why expect it to show up quickly in cultur4e). Of course its rarity in the blood cells does give me pause - it makes me think that it must be present in higher levels somewhere else.

We also learned that altho Lo has not completed the work he wants to complete that he and Alter feel very confident about their findings.

We know you can leave XMRV out and that does not disturb it; in fact it may enhance detection....

We know the WPI's PCR results were not consistent with the NCI's but that their serology results (which they are more familiar with) are....and that both those labs got different results from the CDC/BSRI labs.... How they figure out who was right and who was wrong I have no idea

I just can't imagine Phase II is done....is it completely done? Are they going to start developing assays???

 

[Esther12]

I find the lack of consistency to the BWG results more worrying because the WPI's Science and now UK paper sound so conclusive. What's caused the difference, and the additional problems with the BWG?

Could it be that some sort of contamination occasionally occurs when the blood is collected? That could explain why the test results were positive for certain draws, but not others? Also, it sounds like CFS samples were collected in a different way to healthy controls for the UK study, was this the case for the Science paper to?

Am I missing something, or was Alter a bit of a bust with the BWG? (I'm still not exactly sure what the results were).

I'm putting things negatively here, as it's all so confused I don't really know what to think, but these are the concerns I have following the BWG announcement.

Many thanks to Valb626 for all that typing. Great stuff.

 

[alex3619]

Hi, the issue with getting results with blood draws on certain days could be a useful clue. First, it might mean these tests are sufficiently unreliable that they only work sometimes, because the testing is right at its limits. This would mean that without better tests we won't have reliable blood testing.

Alternatively, it could mean that XMRV is more present in the blood in either cycles or bursts, not continuously. This might mean that using blood will be very limited as mulitple tests will always be required, unless an XMRV component can be identified that is more persistent.

If either of these are true, we need a methodological improvement to be able to mass screen blood. I really think that, for CFS patients and not the blood banks, we might have to move to lymph node biopsies as a more certain way to test. I am not thrilled at the idea for a lot of reasons - any deep biopsy has a risk of complications, even if it uses a fine needle, especially in anybody who is immune compromised.

The alternative is to keep improving the blood tests. Maybe we need antibody tests for specific XMRV proteins, or an antibody panel with multiple targets, or something like that.

I guess the point I am making is that this kind of results could be due to error, but we can't rule out that it an important clue to help us understand what is going on and help the researchers improve their techniques. If I were one of these researchers, I would be burning to know what was causing this apparent anomaly.

Bye
Alex

 

[eric_s]

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.

SH... To hear those lines by this man is very good... Even if youd only take the last 4 sentences. This is exactly what i would have wished for. Merry christmas
Sorry if im posting this now, one day after the event and before reading all of the thread, but this is the best news so far, after the rather disappointing things reported earlier. We have one of the best guys in the world who says its serious and has to be investigated... what a change! So even if XMRV would turn out to be a dead end, which i absolutely dont think it will, we can be confident.
Our work is only starting now, i guess, unfortunately. We will need to raise money, make sure it goes to the right places, advocate, inform, etc. Basically for as long until there is a "perfect" cure... and that might take a while But it will be so much easier with people like Dr. Alters support.

Now ill have to read the rest. Hope we will get a good summary soon, because its hard to make sense of the info for me, so far.

Back in Switzerland now...

 

[anciendaze]

...It's very confusing and they seem to be discussing both mouse and human mitochondrial DNA, in the second post.

The point about mouse mtDNA is that its presence would show that entire mouse cells, including mitochondria, were in the samples, exposing contamination. Discussion of human mtDNA comes in indirectly. They are trying to avoid mtDNA, because it is notorious for variability (low copy fidelity), and they believe the essential pathological process must be in the nucleus. If they could find human nuclear DNA with the entire provirus their task would be much easier.

Hidden assumptions about mitochondrial involvement, or lack of same, are causing disputes. If they also tested for antibodies to cardiolipin, which forms 20% of the inner layer of mitochondrial membranes, they would see that severe mitochondrial structural damage is a good marker for ME/CFS and other conditions where acquired mitochondrial dysfunction is suspected. (Is that damage being caused by virions forming inside mitochondria, and rupturing the membrane?)

I don't understand too much about about mitochondrial DNA... maybe I should do a wikipedia search and have a read about it!

I strongly recommend that. When specific medical knowledge is lacking you must fall back on more general biological knowledge. Acquired (not inherited genetic) mitochondrial disease in humans is still controversial. Some people born with mitochondrial defects survive. You should compare their symptoms with ours.

 

[Cort]

Hi, the issue with getting results with blood draws on certain days could be a useful clue. First, it might mean these tests are sufficiently unreliable that they only work sometimes, because the testing is right at its limits. This would mean that without better tests we won't have reliable blood testing.

Alternatively, it could mean that XMRV is more present in the blood in either cycles or bursts, not continuously. This might mean that using blood will be very limited as mulitple tests will always be required, unless an XMRV component can be identified that is more persistent.

Bye
Alex

Very illuminating Alex...I remember Dr Mikovits saying that sometimes it took multiple tests over multiple time points to find the virus in the original paper. As I noted long culture times are also sometimes required..so the real rarity of the virus has always kind of been evident and that would certainly make it more difficult to find...