Vai al contenuto

Foto

"1st International Workshop On Xmrv"


  • Per cortesia connettiti per rispondere
8 risposte a questa discussione

#1 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 03 settembre 2010 - 15:17:23

Immagine inserita

"1st International Workshop on XMRV: Pathogenesis, Clinical and Public Health Implications"

Workshop information, abstract, program.. visit: www.virology-education.com

Dear Colleague,

It is with great pleasure that we announce a new initiative in the field of XMRV research, the "1st International Workshop on XMRV: Pathogenesis, Clinical and Public Health Implications". This workshop will be held on September 7-8 this year at the National Institutes of Health in Bethesda, Maryland, USA..

The objective of this scientific conference is to assemble an international group of scientists, physicians and epidemiologists to present and discuss, in a public forum, the latest XMRV studies on a range of topics including virus-host interactions, cell type tropism, mode of transmission, animal models and the efficacy of current antiretroviral drugs.

This meeting will offer an interactive setting where the latest developments in the field can be presented in order to evaluate the state of our knowledge, address controversies, and develop an understanding between experts that will help direct future research.

This workshop will be co-sponsored by the NIH and will be organized by Virology Education.

We would highly value your attendance at this workshop and look forward to welcoming you at this very important XMRV Workshop in September 2010.

Kind regards,

The Organizing Committee

Charles Boucher, Erasmus University, The Netherlands
John Coffin, National Cancer Institute, Frederick, MD, USA
Stewart Le Grice, NIH, National Cancer Institute, Frederick, MD, USA
Robert Silverman, Cleveland Clinic, Ohio, USA
Jonathan Stoye, National Institute for Medical Research, UK

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac


#2 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 09 settembre 2010 - 18:17:45

XMRV Conference, Day 1

Head of the NIH Dr. Francis Collins opened the conference with a cautiously optimistic talk. His take on XMRV and related MLVs combined "some skepticism" (largely due to the negative XMRV studies) with "enormous medical importance," if the positive papers win out. As for the FDA/NIH/Harvard paper, Collins said that "differences might matter," referring to that study's findings of four XMRV-related MLVs in CFS patients and controls versus Dr. Judy Mikovits's XMRV finding. Most importantly, he said a NIAID "multi-center study" on XMRV and related MLVs will be done and that he and NIAID Director Tony Fauci had discussed it. Collins closed by saying it was a "very exciting time" and expected "great things" to come out of the discovery.

Some of the information at today's conference was material from papers already published, and some came from papers not yet published that the researchers don't want out until they are published. Frustrating to say the least--but none of today's findings were revelatory. But tomorrow is another day. I'll know more about what I can and can't report tomorrow.

Dr. Ila Singh told me that she'll submit her autopsy study in a couple of months, and will submit her CFS study probably by the end of the year. She wouldn't say what her findings are, but she has a very lovely smile.

Dr. John Coffin was marvelous, talking a mile a minute--so fast that after a while you realize there's no way you'll ever be able to write as fast as he can speak.

I chatted briefly with longtime CFS and HIV physician Dr. Nancy Klimas, who gave a word of caution about CFS patients using antiretrovirals, as they're known to mess with the cells' mitochondria.

One light moment that had most everyone laughing came when one of the presenters, Dr. Ikeda, calmly bemoaned that the mice he used in his experiments were very aggressive, lightning quick, with the troublesome signature of "pretending to be dead when handled."

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac


#3 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 10 settembre 2010 - 13:04:32

1st International Workshop on XMRV Q A Wrap-up Session on You Tube:

Sono online i primi 9 video della conferenza:

http://www.youtube.com/view_play_list?p=C48EFC7D6D7F217A

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac


#4 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 10 settembre 2010 - 23:54:49

Transcript of the 1st International XMRV Workshop Q&A
pubblicata da XMRV Global Action il giorno giovedì 9 settembre 2010 alle ore 10.45


Here is XMRV GLobal Action's "close" transcript of the Question & Answer session from the 1st International XMRV Workshop. Please feel free to link externally, with credit and hotlink to our XMRV Global Action team. Enjoy!


XMRV Global Action’s “Close” Transcript

1st International XMRV Workshop Q&A session

Video may be available here when uploaded: http://videocast.nih...tEvents.asp?c=1

We'll post the link as soon (and if) an official transcript becomes available from the NIH.

Kirsten White from Gilead Sciences

My question is about the different clades of potentially human pathogenic XMRV’s. We heard about the X and the P, and I was hoping you could summarize, are there four we’re looking at, are there two, are there three, and what we should call them.

Dr. Jonathan Stoye, Panelist & Moderator

Let me start by saying this is probably one of the questions I’d hoped would be answered by this time in the proceedings. What I’m not certain is whether I’ve had it clearly answered whether we’re dealing with zero, one, two, or possibly more pathogenic agents…

Dr. John Coffin, Panelist: Clearly multiple sequences have been identified, , particularly in CFS patients, and in some cases in normals. As yet, we can really only refer to one virus, and that’s XMRV, and that’s only one of the sequences that we know is in a replicating viruses. And I think it’s v important to keep that in mind. We don’t know what if any virus the sequences that match in to PMV or MPMV clades other than XMRV, what their biology is. We only have complete sequences (for XMRV) – Jonathan asked earlier for example about the LTR’s that go with these, that’s the question I’d be very interested in because the LTR’s of the PMV group and the MPMV group are actually quite distinct from those of the XMV group of endogenous mouse viruses and we have long hypothesized that there’s a little insertion sequence in there that actually renders them potentially quite non-infectious although that’s never been directly tested. And so I think clearly a bunch of different sequences. I think before we start referring to a bunch of different viruses we really need to have viruses that go with those sequences. We can say there are sequences there that look like endogenous MLV’s, maybe a little bit different from them. But we just don’t have a virus yet to go with them.

Dr. Frank Ruscetti. Can I follow up on that Jonathon. I agree exactly what John says. I’m trying to see if these are transmissible. It’s sort out of my league, do you guys have any suggestions about the best way to look for some poly (tropic virus) that’s never been really transmissible in a mouse, could be transmissible in human cells. Do we just take a shotgun approach? Do you think?

Dr. Coffin: Sounds like classical virology to me… (laughter) But a complete sequence would be a good start.

Dr. F. Ruscetti: Sounds like a policy statement to me. I understand that. Do you think it’s going to have to be a recombinant from what we know about the mouse?

Dr. Judy Mikovits, Panelist: We actually have at least 500 isolates in LNCAP cells and in PBMC’s where we have the opportunity to put funds into getting complete sequences of whatever viruses is in there

Dr. (indecipherable): “You can’t do that”

Dr. Mikovits: “I know you can’t do that”. – but I think that’s a reasonable approach for starting, if you have natural isolates and you know they’re there, let’s start sequencing the entire genome..

Galen Marshall, U of Mississipi: I hope this is a science question, but it has policy to do with it, so hear me out before you cut me off. I’m Galen Marshall from U of Miss. The question I have, I’m an immunologist, I’m not a virologist….

MISSING TRANSCRIPTION SEGMENT –

REALPLAYER MALFUNCTION! ESTIMATE 5 MINUTES MISSING.

We'll fill this in asap

Cont’d……..

Dr. Jerry Holmberg, US HHS, Panelist:… the sample preparation. We don’t have all the data to show you and share with you, but at least we’re trying to standardize even with the sample prep and the time to processing. And just that alone may help us. But there’s a lot that we can do and I think that through this Blood Working Group that we can standardize some things.

Dr. Coffin. You have to be reminded that it’s been less than a year since people, most of us have been seriously thinking about dealing with these issues. It’s really quite a short time. It takes a long time, to set up, say to set up the blood working group panel, it’s been probably six months of talking and deciding and so on before we began to get samples really in… so it’s only couple of months that we’ve been working on that. So I’m quite optimistic that say within the next year there will be a synthesis of this to the point where not necessarily everyone’s using exactly the same assay – you don’t do that with HIV – you have different assays designed for different purposes. And I think we’ll head toward that fairly quickly now I would predict. But right now we’re still in a zone of chaos where since we don’t have agreement on almost anything in this we have to work toward that right now. But I’m optimistic we’ll get there soon.

John Mellors, Chief of Infectious Disease, U of Pittsburgh I’m a virologist. I may get bounced for this because it’s more of a statement than a question. I am struck – and I’ll restrict this to CFS - by the highly divergent prevalence of detection of anything (his emphasis) among cohorts with CFS. And it’s really very striking sitting here the day and a half, from 0% to as high as 70,, 80%. Part of the problem could be different patients are being studied. Part of the problem could be different detection methods. I propose a simple way to add clarity. And that is the same patients to be tested by multiple laboratories. The blood working group has started this, but their primary concern is the safety of the blood supply. This leaves patients with the syndrome and healthy controls in the lurch. And I would propose that there be a collaborative group putting together patients with the syndrome and appropriate controls that are agreed (his emphasis) upon, and that a neutral party take those individuals, draw multiple samples from those, and store them as a repository to then be distributed to the laboratories that are part of the working group or additional ones. Unless we start testing the same patients with different methodologies, we’re not going to get anywhere. And I really want to emphasize that to resolve this discrepancy between 0% and 80%, we all have to be testing the same samples. And I’d like to know among the panel and the audience what are the plans for that?

Dr Holmberg: Well let me just say about the Blood Working Group, and I think that this is one of the goals of the clinical panel that you heard Graham talk about. Is that through the clinical panel we will be able to characterize some of those positive donors – or I should say patients. The thing is we have relied very heavily on Judy and we have, you know her sample population. And I think the thing what we have to do is we have to make sure we have a good cross section. I agree that there’s a lot of patients that come around the world actually to Judy’s facility. But I think that we really need to see a geographic distribution of this. And I agree totally with you… I think that one of the things that I heard a lot in the last couple of days was the lack of a standard. And I think that that’s something else that hopefully we will have as an outcome of the BWG and some of the panels that we’re trying to establish.

Dr Mikovits: We saw at this meeting several posters and we heard from 4 physicians, Dr Cheney, Dr Bell, Dr Peterson, Dr Komaroff on the Lo study. These are experts at the diagnosis of, and they are diagnosing the same patients generally and we saw the same percentage of positive patients in those. Those are patients geographically located from as you heard Dr Cheney say, from around the world… from the NE US in the case of the Hanson-Bell study, I know that Nancy Klimas gets a lot of patients form Florida. So we can begin to address that because there are clinicians that have been identifying similar positivity rates so we can pull positive samples from each of those and really begin to put together literally hundreds to do that very thing.

Dr. Ann Sing (?) – Cancer epidemiologist specializing in prostate cancer from the NCI.

I’m here to learn whether the XMRV assays are ready for prime time because we have a lot of cohort samples that we bank away ready for etiologic investigation... So I just want to reiterate the importance and echo and underscore the previous person from Pittsburg… the cross validation of these assays is extremely important because if we look at the HPV research, in the early age of HPV research, there was a struggle of HPV detection and once that was validated and clear, there was tremendous progress in HPV research and then there was the HPV vaccine development. And for XMRV if this is related to prostate cancer, cancer epidemiologists cannot do anything until we have a highly sensitive and specific assay in order to establish causality association, and also to establish prevalence, natural history of XMRV infection infection. Epidemiology. Of XMRV infection. All of these is dependant on highly accurate, sensitive, specific assays. So some sort of coordinated effort among these laboratories using different assays, different platforms, I think that will make tremendous contribution to the field of XMRV research. So I really encourage you to work together. Another example is in the GWAS genetic research of prostate cancer for the last 3 years that all of the studies and consortium came together. And so we have GWAS, and the least 3 years the progress that we made in genetic research has actually surpassed what we have done in the past 20 years. So some kind of collaboration and coordination I think would really make this field move forward much faster, and I am looking forward to that.

Dr. Stoye: If I could just say to the gentleman, the immunologist who was complaining about the virologist… I think it does seem to me that we are moving towards a situation whereby around the nucleus of the Blood Working Group there will be defined assays, and it will happen very very quickly, so I share John (Coffin’s) confidence that in a relatively short period of time we will be able to give you the answer to the question that you were originally asking.

Dr. Jonas Blomberg , Uppsala U, Sweden. Part of the confusion may be due to sequence biosis of the nucleic acid-based tests. It strikes me from Dr Kosak’s talk where she demonstrated an “iron curtain” going right thru Europe of having different viruses in mice. That could also be reflected in the patients. So we might have to have assays that detect stuff that’s on the north of this border, and another test for those who are south of this border. So we must understand much more of the basic science. And it strikes me that the Derse assay which is only dependent upon packaging may not have this sequence bias, so it could be used much more as a sort of a golden standard.

Dr. Stoye: – I don’t think that it’s an assay that in the long range can be a golden standard. Anything that involves multiple (packaging?) pathogens cannot be. We have to develop an assay that will give us either antibody or PCR in order to screen large numbers of people. … Now that assay may help us towards that aim. But the long term goal must be a PCR or serological assay.

Joe – clinician – I also want to support the comments from the person from Pittsburgh. I have a question because the golden standard that is normally presented during these presentations is the CDC or the Fukuda criteria, but are there data on the performance and the variability with doctors using these criteria? In other words is it conceivable that one doctor would rank a person “in” and another doctor “out” (of these criteria)?

Dr. Mikovits: Yes, the criteria are highly variable and probably some of the physicians in the - they’re really, really subjective, and unless if you look for various immunological defects rather than just subjective defects, that you get a lot closer to seeing what we see in our patients, the patients that we identified in UK in the London area, and what Drs Bell and Komaroff are (seeing)…

Dr (indecipherable): If that’s the case, if you’re going to compose clinical cohorts I think it’s important that you have different clinicians selecting and that you also create some data of other doctors looking at the same patient and confirming whether a patient is in or out.

Dr Mikovits: Well they’ve been looking for that for decades, biomarkers and things that could help better define this disease because it is so heterogeneous in how it’s defined.

Dr. Joe Barrascano, Clinician. Over the past day and a half I’ve been struck by the consistent inconsistencies of the results. In other words the groups that find the virus find it in 2/3 or ¾ of patients, and maybe 5% who are not. And then there are groups who find it in absolutely nobody. It’s very important to work out methodology and so forth. But I think what could explain this tremendous difference that is consistent. And I think it might go one step before. Maybe it’s the collection and storage of the blood prior to processing that’s really causing the problem here… because if it were a methodological problem you’d see variation from 1,2,10,20,40,50% rather than zero or 80%.

Dr. Mikovits: Actually that is true Joe, and … we have learned literally in past 2 wks in the BWG that processing may be a key and we may have found an opportunity to have a processing protocol where everyone would at least find viral RNA in plasma and blood products without culture.

Mindy Kitei, Journalist – My question is about treatment because that’s what people who go to my blog want to know. When are we going to start drug trials, what drugs are going to be used? Monotherapy, triple cocktail. Where, when, why.

Dr Coffin – It’s really premature right now until we have some handle on the pathophysiology and association of the virus with disease. One has to be aware of why anti(retro)virals work against AIDS – because they block HIV replication. The continuing pathogenisis of HIV in the case of AIDS is due to constant replication cycles of the virus over and over and over again. And as it turns out, quite surprising, as a long-term retrovirologist at the time AZT was brought into the clinical arena – I was quite surprised because no other virus infection behaves in this way that we knew at the time. It’s only because of that over and over and over replication that any antiviral works. We have no antiretroviral drug that does not require constant virus replication for the pathogenesis of the disease to be effective.

Right now in the case of a disease like prostate cancer I think we can be reasonably confident that that’s not the case: that the ongoing disease, once diagnosed, is extremely unlikely to be dependant on continuing cycles of virus replication. Once the cancer arises, the cancer self-propagates without the need of the virus. Every model that we have for retroviral cancer would be in agreement with that idea.

In case of CFS, CFS resembles a disease that might have the potential for virus replication to be involved in its etiology, so that’s a very good piece of news if the virus is in fact involved in the etiology. There are arguments among reasonable people that going into a set of trials like that could actually provide that kind of evidence. But until we have a good way to assess the virus, what’s happening with the virus. We don’t even have a good way to assess what’s happening with the virus just in static cases of the disease. There’s so much disagreement about what’s going on. There aren’t quantitative - none of the assays involved are in any way of the sort of quantitative assays one would need to do this. Until at a minimum we have that kind of information it’s really premature to think about treating the disease with antiretrovirals.

Mindy Kitei: Well, how long will that take?

Dr Coffin: And it’s certainly and I will make this case again – it’s certainly counterproductive to just go in and do ad-hoc treatment, off-label treatment of patients with ARV’s right now and collect anecdocal evidence of a disease that we all agree is subjectively defined, and has an alternating course. We will learn probably less than nothing from the anecdotes that come from that kind of off-label treatment.

Hillary Johnson – I would love to hear Judy Mikovits answer the question about antiretroviral treatment if she doesn’t mind.

Dr Mikovits – I do mind – I can’t answer that.

Dr. Roger Dodd – American Red Cross – I’ve been sitting here and I’ve heard a lot of almost incompatible information coming across and a number of potential high-level hypotheses for why we are seeing or not seeing why we are seeing or not seeing it. For example we’re not diagnosing the patients in the same way, we’re not all doing the tests properly. We’re seeing different mice. But I’d like to ask the panel to speculate on some plausible mechanism that might suggest some of the variability that we see, beyond those rather technical reasons. I’ve heard a certain amount of virology. We’ve heard this virus may have entered human populations tens or thousands of years ago. So what would we speculate on as a panel of what’s really happened. Or is it too early?

Dr Stoye: I suspect that until we have the technical details sorted out – and I honestly believe that at least some of that reconciliation will take place in the relatively near future, I don’t think we can address some of the more interesting ideas.

Dr. Don Blair, NCI/NIH, Panelist: I would just say that from other, from carcinogens and things like this, many people are exposed to carcinogens and not everyone gets cancer from that. I think the host, the genetics of the host - a lot of things which we certainly don’t understand about cancer’s initiation and I’m sure is equally true for CFS and others - are things that can influence this. But as you say, at this point we don’t know enough to even begin to get at those questions.

Dr. Francis Ruscetti: I certainly agree with John (Coffin) that it’s premature to envision drug studies. But what fuels that is a practical thing called funding. So you’re involved in the extramural program of the NCI. Is there any plans… What would it take for the NCI to increase funding in this area.

Dr. Don Blair, NCI/NIH: I knew someone was going to ask that question. Why am I here? Obviously there is a great interest in the NIH and NCI in this whole area. The fact that the director was here and listening to talks and asking questions I think is an example of that. I think that we and certainly people in our division are watching this whole area and trying to decide what is the best way to stimulate it or perhaps to do something. Right now it’s not clear what that is. This as I think somebody said hasn’t been around for very long. The number of RO1 applications that have been directed is still pretty small. And the mechanism that exists to generate research funding by submitting good ideas and submitting things that will go through the normal process is there. And that is obviously the initial way to do this. As things develop and it becomes a little clearer what’s going on I think then certainly I would suspect that the NCI and NIH are going to look and see if there are things that would be appropriate to do - and if the money is available.

Dr. Ruscetti: To follow up on what the man from Pittsburgh said: It would seem to me that the best way to help that is multidisciplinary P01’s, multidiscipline sort of things, and that requires some level of discussion in the levels that I’m not privy to.

Dr. Blair: The mechanism for multi PI grants, R01’s – as well as larger P01 projects exist – and these are all investigator-initiated. All you have to do is to put together a P01 project that’s focused where the sum of the project is better than each individual project by itself, and you can talk to program people who can advise you on how best to do that. So those mechanisms are out there and they are being utilized. There are things that are utilizing that, that will address some of these questions. And we would certainly encourage people to use them and apply.

Dr. Coffin: If you look around this room and consider the number of people that we had to turn away because we didn’t have room for this meeting. The number of people that have jumped into this field and diverted their own resources for what they had in their laboratory for all of their other grants, both extramural and intramural. NCI has not put any extra $ intramural money for this purpose – Yet an enormous amount of work has been done and a lot of funds have been diverted by all of us from our previous projects into this area. I think this is remarkable testimony to the resilience of American, European, international science, that in fact that we can do this without the necessity for instantaneous top-down funding.

However the momentum on this will tend to run out after a bit without additional money being put into it at some level or another. So it’s very important to sustain the momentum that we have so far. We will need to find funding mechanisms, whether traditional R01’s or RFA’s or whatever that will allow this process to go forward.

Even though right now this is a real zone of chaos, I think any new scientific field goes through this, and I think we’re just seeing what is kind of the normal sausage making – early stage in the natural scientific process. And I think it’s proceeding along quite well actually, quite frankly.

Dr. Angelo Demarzo, Johns Hopkins, Pathologist and prostate cancer researcher: Just to be slightly different and not to sound heretical. But I actually think the number of negative studies is actually precluding or scaring off a lot of people from probably doing things like R01’s. One of the things that is different now, PCR is an exceedingly sensitive assay as we know, and you can actually get false positives. But the fact that people come up and say I have zero out of 500, zero out of 100. Other people are saying, when something is really there that prevalently, and if it’s really associated with disease, 80%, I think a lot of us would think, “It wouldn’t be that hard to find”. And an example in prostate cancer there was a fusion gene discovered several years ago, a science paper, and within a year there were 17 or 20 confirmatory papers. Every single lab that tested this – found it - it wasn’t that hard to find, it was RTPCR to find. And so the question is, are some people being scared away because of the negative studies. And if that’s true, why are so many studies negative when we have such unbelievably sensitive assays. These are not just based on antibodies that cross-react in a way that’s kind of weak. These are based on the Swedish study, the 2 German studies – I thought they were very compelling.

Dr Mikovits – Well I think because all of these studies are focused on primarily PCR and that’s not how we classic retrovirologists have identified either of the other 2 human retroviruses, particularly not HTLV1 which was so difficult to find, so cell-associated. We’re talking about DNA hypermethylation of these viral genomes in cells so that they’re not expressed. So when you use complementary methods as we did 25,30 years ago, when we did most of the work in HIV and HTLV1, we used all of these methods to increase the power of the finding, not just a simple PCR.

Dr. Myra McClure, Imperial College London – I can’t agree with that Judy. I mean, a lot of us have done the serology as well. We would isolate virus if we could find positives. We can’t find positives, we can’t get the virus. But certainly the serology is backing up our PCR. And I frankly don’t know what else we can do.

Dr Mikovits – I had at least 50 positives right from the London area and many more besides that using the techniques that we validated in our paper and clinically and that have been used throughout this room.

Dr McClure – I’m very happy to be proved wrong if people can send positives but what I said to you when you very kindly offered to send me some positives to my lab. They have to be independently sent.

Dr Mikovits – And we agreed to do that, to have phlebotomy services send them directly to you.

Dr McClure – Well I’m happy to do that now. But at the time you wanted to send reagents from your lab to mine.

Dr Mikovits – Well the monoclonal antibodies and the antibodies that have been validated, the 7C10, I haven’t seen the other assays clinically validated to detect a clinical sample. They are very highly specific against expressed XMRV proteins from VP62, a reference standard that, you know, so far hasn’t been detected in a natural isolate as prevalently as some of the other variation that one would expect in a retrovirus.

Dr McClure – I don’t quite know….

Dr F. Ruscetti: Today we saw reasonable things from the FDA and the CDC. All right. One found positives where the other found negative… and another found negative where the other found positive. And they still used validated tests. We do not know at the moment what the difference is – if it’s processing or whatnot. But I stand on the recommendation that I made, until we understand it better: Negative PCR is not a stand-alone assay for detection of this virus in clinical samples.

Dr. McClure: I agree with that. (indecipherable) No, we have. We’ve now done the serology. Sorry.

Dr Mikovits: No we have.

Dr. Steve Kleiman AABB, Transfusion Safety area– I have a question about the general topic. Accepting that we have positive results in both prostate cancer and in CFS. One of the unifying hypotheses to begin with was that both of these diseases have a mutation or people with these diseases might have mutation in the RNase pathway. But what we’ve heard is that most of the studies that have explored this is that there is no predilection for RNase phenotype, and so the original reason why maybe CFS and prostate cancer would be the two diseases one would search for a presence XMRV doesn’t really seem to exist. So my question is, can the panel speculate on why this virus exists in these two conditions – are we talking about immunosuppression, passenger virus.

Dr. Mikovits: First I want to say, and I know that Bob said this yesterday. We were looking at single snip that was in original study, but there have been defined by biological assays and functional assays, other defects and that’s what both Bob and Dr Lombardi and our group have submitted numerous R01’s to understand what is the defect in the RNase-L type 1 interferon pathway is … and those are the kinds of studies that can find and answer those types of questions. What is it about the innate immune response?

Dr Stoye: I think it’s not unreasonable to speculate that the individuals in which these viruses take, do have a defect that might be other than the RNase-L one that we talk about … or it may just be an environmental affect that means their immune system is temporarily suppressed.

Dr. Coffin – I mean it’s still possible to entertain the idea that the disease causes the virus, and not other way around in a sense... or makes visible a virus that’s actually very prevalent, but it’s really such a low level in some, couple of cells somewhere in people, it only comes up because of the conditions surrounding these diseases…

Dr. Mellor: So just to shift gears a little bit. I’d also like to make a plea that CFS and prostate cancer be separated as follows. The epidemiology of putative XMRV or other MLV acquisition related to prostate cancer may be completely different from that of individuals with CFS. For instance you go on the internet and look at what types of therapies that individuals with CFS can acquire – and that’s in the public domain – it’s frightening. And what is given to them behind closed doors in desperation it leads the imagination astray to wonder what’s actually happening– and could there be a completely different microepidemic being transferred parenterally with CFS that has absolutely nothing to do with acquisition of a retrovirus related to prostate cancer. So I really think we have to draw a line and not say the epidemiology is the same for both entities Nor, most of us would agree the pathogenesis is not the same.

Dr. Stoye: But is anybody saying the epidemiology is the same?

Dr. Mellor – There are allusions to that when what’s found for CFS doesn’t match what’s found in prostate cancer, that the two, the disease process is incompatible with the same pathogen. And what I’m saying is that there are multiple ways that infectious agents are being transmitted with different disease manifestations.

Dr. David Wilford, GSK – My question is to Judy but other people are looking at detection of XMRV. Before the XMRV studies, specifically the Virochip showed I believe that there were multiple viruses present in some of these CFS samples. I’m just wondering with these XMRV positive samples if we’ve being looking specifically at serology or PCR for other types of viruses being more reactivated than controls or if anybody else there is doing these XMRV studies looking for other viruses, or just specifically for XMRV.

Dr. Mikovits – Yes, we set up this program as a study to look at all the viruses, because CFS patients have a lot of activated things like CMV and HHV-6a herpes viruses, mycoplasma, Lyme. So the idea in the beginning is, as with HIV-AIDS that the retrovirus creates an underlying immune deficiency as-yet-unknown, allowing the immune system not to be able to control pathogens the rest of us can control, because we don’t have that underlying immune deficiency. So that what we see is the sickest of the sick, the tip of the iceberg, as in the earliest days of HIV-AIDS, where we saw Kaposi’s Sarcoma, pneumocystomonia and the other 25 AIDS-defining illnesses. So that is the hypothesis we’re following. And we’ve developed chips to look at all the Herpes viruses and pathogens in correlation with expressed virus in our patient population. . bec we don’t have that underlying immune deficiency, we’re seeing sickedst of the sick. We’re seeing tip of iceberg – so that is hypothesis we’re following – we’ve developed chips to look at all the herpes viruses and pathogens in correlation with expressed virus in our patient populations.



Dr. Wilford – What I’m worried about, is XMRV the cause of this immunosuppression or is it just another of these viruses that is being expressed.

Dr Mikovits – Retroviruses are not ubiquitous and they’re not generally benign – so the kind of biology that we’ve looked at with HTLV1 with the HTLV1-associated myelopathy and the acquired immunodeficiency virus, HIV. That’s a reasonable hypothesis. So it has not been a passenger in the other human retroviral-associated diseases so there is no reason to expect that it would behave other than another human retrovirus. But of course this is the first human gammaretrovirus. So Sandy (Ruscetti) knows in that family of viruses the envelope is both an oncoprotein and a neurotoxin. We heard yesterday about HIV creating a dementia distinct from the immune deficiency based on the viral envelope protein, so these are all hypotheses that we’re following.

Mindy Kitei: My question is about the –ve studies for CFS. And I understand Dr Coffin you say,”We still don’t know”. But having read these and having reported on this disease since 1994. The negative studies, many of these patients in (Empiric definition) CFS don’t have CFS in these studies, they have depression. And Dr Leonard Jason has done studies on this, that the Empiric definition that the CDC uses, 38% are depressed. So you’re not even dealing with a cohort that has the disease. And I think that that’s really important instead of saying, “We don’t know yet”. Which we don’t know yet. But there are patients who have been desperate for 20, 30, 40 years… and I understand it’s premature to do these drug trials, but we also have to call a spade a spade. And when you have a study for instance by the CDC and they don’t find it (XMRV). Ok. And then they want the RKI in Germany to confirm. RKI in Germany didn’t find it in prostate cancer. Why not, Mr Switzer, go to the Cleveland Clinic, who did find XMRV. You know, you seek what you want to seek. And I think it’s important that we really see things as they are and not how we want them to be.

Dr Stoye: I think we’ve heard enough of this particular line of questioning. I think nobody in this business is trying to get a negative result – it’s in nobody’s interest.

Mindy Kitei: Of course it is.

Dr Stoye: Not one of the (indecipherable) here wants to give a negative result. And I think it’s incorrect to suggest that’s the case. I’m not going to go into questions about the CDC. Or policy in Britain. But I think it is wrong to suggest that people are trying to get negative results.

Mindy Kitei: The CDC has said this is a psychogenic illness for 26 years. So for them….

Dr Stoye: We’re not here to discuss the CDC.

Mindy Kitei: OK. Ok.

Dr. Coffin: Given the kind of heterogeneity you’ve just described is all the more reason that you just can’t launch into willy nilly therapeutic trials where there may be 10 diseases. You know 10 patients come in, only one of them might have the disease that’s caused by the virus. You’re not going to learn anything by treating all 10 the same way. You have to sort all that out before we can start.

Mindy Kitei: I totally agree.

Dr. Coffin: I agree we should all work toward that. But we’re nowhere near that right now. Maybe we can get there faster. I hope so. I hope we can get to that quite fast. Because that point is available to us.

Mindy Kitei: I certainly do too.

Dr. Coffin: We’re certainly not there now. We can certainly start to think about how we would do such a thing if we were there. In the meantime, people should really lay off these drugs.

Female X: I would just like to clarify something that was stated earlier, and that is that you don’t often find retroviruses lying around infected people or animals that don’t cause diseases… in fact there’s a virus I studied – gibbon ape leukemia virus – Most of the gibbons in the zoos of the United States are infected with this virus. There are no neoplasias. There is no disease associated with it…

Dr. Michael Sniderman – Buffalo, Med Oncologist – I know that the medical people are going to say this is a passenger virus. And since you can’t give the virus to a person to reproduce the disease, and fulfil Koch’s postulates, how do you expect to answer this question if you don’t do an interventional study and show improvement? How would you do that?

Dr. Coffin: In the case of HIV infection and association with AIDS, giving the antiviral and showing that improved the disease was a major argument showing the causal relationship between the two. But by time that was done there was a very good basis in our understanding of the virus infection of the disease which was then moved forward by the result of therapeutic intervention. We cannot at this point… And if we were to see a continuous measurable association of the virus that we could quantitate and that we could show correlations, like the amount of virus with severity, and a quantifiable assay in easily assayable manner, then it would be time perhaps to start to think about these trials, even ahead of – and my colleagues would probably disagree with this – even ahead of having a clear Koch’s postulate type of proof of association of virus with disease. But we’re not at that point now so it’s highly premature to even think about that.

Dr Stoye: At least in the case of HIV, you had examples of the hemophiliacs who were being transmitted and coming down with disease. So there, in fact you had got much closer to fulfilling those Koch’s postulates.

Dr. Coffin: That kind of epidemiological association actually would go a long way. And maybe we’ll be able to get that once we’ve agr – once we can find assays that are consistent and that we have some sort of consensus on.

Dr X: One thing that you didn’t mention but that I think is important to mention here is that progress with treating HIV came also thru mistakes we have made in the time where we only had single drugs. We lost people who were on monotherapy who developed drug-resistant virus and later could not be salvaged by the combination therapy because they had multiple drug-resistant virus. So I think there’s a potential side-effect of going into individual patient treatment with single drugs and that we can learn that in the future if the drugs are going to be successful, we may have weighted options. So you need to understand of what the drugs are doing in parallel if you’re going to get xxx for clinical trials. .

Dr Coffin: In terms of our advancing knowledge though these patients did not die in vain. What we learned from them very rapidly led us to understand what we really needed to do to treat the infection. Without that step I don’t we wouldn’t have gotten to the point where we are in HIV.

Dr X: But the question is do you want to make the similar mistake again.

Dr. Holmberg: I think that we learned a lot from the HIV epidemic. I’m saying the blood community. And as was already mentioned, I think that definitely the hemophilia community took the brunt of it. Clearly they were the canaries in the mine. But I have to say that one of the things that we learned thru the HIVexperience was that we needed to start having repositories and that it was thru the insight of NHLBI that we started the REDS studies and we were able to do and put away the repositories. I don’t know if you appreciate the slide that Graham Simmons presented, on the different repositofies that are out there. Some of those repositories are linked between donor and recipient and this is a powerful tool that we can tap and identify has there been a cause, and what’s the epidemiology of the XMRV.

Dr. Mellors: So to address the issue of clinical trials, you can take a multiple stage approach. What you don’t want to do is enroll a highly heterogeneous patient group with an unknown prevalence of a pathogen, and assign them to treatment or not. Because any statistician will tell you that the power of that trial to detect the difference depends on the prevalence of the putative pathogen. If it’s zero percent as we’ve heard, or seventy percent, we could either have either zero power or high power. So this idea of assembling a group of patients, a cohort of pts with CFS as well as controls, and defining by standardized collection, by a neutral party, the prevalence of XMRV, and whether it can be or the other MLV’s whether it can be quantified, goes a long step toward potentially identifying a pt group who could subsequently be enrolled in a clinical trial if there’s something to measure related to the virus. If we just start willy-nilly treating or willy-nilly randomizing – without defining the prevalence of the pathogen, we’re going to get nowhere, other than spending a lot of money, employing a few people, and then like the census workers, have to fire them.

So I think it’s really a step-wise approach:

- Define the prevalence of the pathogen

- Focus on those with it

- Determine whether it’s quantifiable

- Do initial phase 1-2 experiments to see whether you can alter the level of the pathogen short-term and then longer term treatment to see if there’s a clinical benefit.

Dr Mikovits: So I’ll just comment on that. So I think that what the group back there and what we were saying is, we have identified hundreds of certified XMRV +ve people, from whom we have isolated the virus, who are very sick. And I think that the commentary that accompanied the paper last week, the Lo paper by andy mason – in those pts who have been bedbound, have not left their house, have not had a life for 25 yrs, the benefit far outweigh the risks of multiple therapies that we have used for now more than 25, 20 yrs in HIV-infected individuals.

Dr. Mellors: I think you’re on the right track. But I think that what’s really important in this field Judy is for your findings to be validated independently so that there are a couple of sources that agree upon your findings so that there’s not the underlying skepticism generated by 0% prevalence in people who are bedbound. And we’ve heard several examples of that. And so yes, you’re right. But it needs to be extended beyond WPI to different groups.

Dr. Mikovits: We have independant confirmation from 3 groups doing those studies you heard of today in several posters that were not from the WPI. But the patients exist with XMRV, with disease. And if we could put something together with them in advance of the larger prevalence studies. They’re infected, they’re ill, they have what you’d expect from a gammaretroviral infected associated disease – and we could begin to do clinical trials, where we crossed over infected people, and switched the drugs and looked for benefits and followed markers, followed infectious virus by assays like the Dersey assay, we’re getting more sensitive assays, serology assays, learning about the immune response, learning about the inflammatory cytokine and chemokine profiles that we have associated with these infections. There are significant numbers of very sick people with this virus in whom these things could be started.

(Applause)

Dr. Coffin: I think, given reproducible association of the virus, quantifiable, a quantitative reproducible assay for virus of some sort, in a patient cohort. Conceivably within that cohort it might be possible to design- initially as John proposed, maybe very small scale studies, just to look at the effect of biomarker of antiretrovirals. It may well be possible to progress fairly soon.

I don’t think Dersey or infectivity assays, given our experience with HIV - will be really going to be suitable for the kind of biomarker monitoring that you want. You really need a quantitative nucleic acid assay –that you can show from time to time in the same patient gives you reproducible results. Results with a dynamic range to follow what’s happening to the virus, just as we can do for HIV.

Given that, it might be worth certainly talking about a very small scale, doing perhaps crossover studies as you suggest, a few wks on, a few wks off, see what happens to the virus, and try to monitor clinically what’s happening to the patient although it’s quite difficult, although my understanding it has to be quite difficult. One HAS to be able to monitor what’s happening to the virus, and for that you need a reproducible assay that everyone agrees is doing it right. And maybe we’ll get there – maybe we’ll get there in a few months.

If we could get to that point, I would not be averse to doing very small scale studies under very tightly controlled clinical conditions and watching what happened as a 1st baby step into this. But without a very well controlled analysis – I think giving drugs to patients individually off-label is extremely counter-productive. Maybe that patient will feel better, maybe that will help. But you’re not going to help anybody else with that.

There are 4 million infected individuals. Uh 4 million affected individuals. None of them will be helped by this. No regulator will accept those results. No 3rd-parrty payer will accept those results. You just don’t get anywhere with that kind of off-label treatment.

Dr Stoye: I think we’ve had enough on that particular subject. Are there any other issues that people would like to raise?

Dr Han? (indecipherable NCI Frederick)– I have a naïve suggestion. . We know that in HPV there’s high risk types, low risk types, and HPV can be detected 100% in cervical cancer. Also we know that human hepatitis B virus can be detected in liver cancer. For this, prostate Ca and CFS, probably you can never reach 100%. My naïve suggestion is that if you really want to prove XMRV is the causative agent of prostate cancer, you really need to establish or develop an animal model that under certain genetic background you can induce prostate cancer. Under certain genetic background. That you can now cause some tumor suppressive gene or activate some cancer gene. That in certain optimal conditions you can induce prostate cancer. Otherwise is very difficult…

Dr Stoye: So how much effort should go into trying to develop better animal models for prostate cancer?

Dr Han? There must be someone who has this type of technique. If some genes are necessary for prostate cancer- over 50% of prostate cancer patient, they have this chromosomal translocation – that genetic background predisposed the patient to XMRV infection.

Dr Stoye: Bob, do you have any views about that.

Bob ?: I mean there are lots of animal models for prostate cancer – going back to the tramp mouse which expresses the SP40T antigen and the probascent (?) promoter. I mean, prostate cancer biologists have studied this for years. The question is whether you can get a specific model for XMRV – I know people are working on it, we’ve heard about some of it here at the meeting.

Dr McClure: I was just going to make the suggestion that you should recruit the man from Pittsburg here onto some strategic committee for future studies.

Doug Jolley, Tokagen in San Diego So HTLV1 was invoked as an example of a retrovirus that causes both a neurological disease (Tropical Spastic Paresis) and a cancer. Does anyone understand how that happens? Does anyone understand why it has those two different outcomes? And has that anything to eliminate XMRV?

Answer (unknown) Kathy? We still don’t fully understand that. We still don’t fully understand white (blood?) cell diseases after all these years, that’s a good point.

Dr F. Ruscetti: But the point is that’s interesting, that has an oncogene that people agreed to that is involved in both of those diseases. And still we don’t have any information as to why it causes the cancer or the immunoinflammatory disease. And we have the molecule that’s involved in it. So…

Dr Mikovits: Do you have some effective therapies around the world for the neurologic component.

Dr Ruscetti: Heavy sigh… Define effective

Dr Mikovits: (inaudible) study where…

Dr Stoye: That’s enough.

Close of Q&A

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac


#5 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 11 settembre 2010 - 00:03:13

Dr. de Meirleir's poster at the XMRV Workshop.

demeirleir.pdf

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac


#6 Falco

Falco

    Grande amico del forum

  • Utenti
  • StellettaStellettaStellettaStellettaStelletta
  • 1.368 messaggi

Inviato 11 settembre 2010 - 08:17:00

grazie. ;)

#7 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 14 settembre 2010 - 00:25:01

XMRV Conference Recap

It’s difficult to characterize two days of talks in a few paragraphs, but one thing that resonates is the, at times, testy battle between two camps of scientists. The cohort that believes that mouse retrovirus contamination accounts for the positive XMRV and related murine leukemia viruses studies was pitted against the cohort that believes contamination has been ruled out and that the positive studies show a clear link between this family of retroviruses and Chronic Fatigue Syndrome and prostate cancer. Not surprisingly, the discussions around CFS grew more heated than those around prostate cancer. Dr. Mary Kearney of the National Cancer Institute may be the one to resolve this issue, as she reported on a test that discriminates between mouse retroviruses and XMRV with, she said,100 percent accuracy.

Read more: www.cfscentral.com/2010/09/xmrv-conference.html

"This article is copyright CFS Central 2010. All Rights Reserved."

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac


#8 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 14 settembre 2010 - 17:06:32

1st International Workshop on XMRV: Q&A Wrap-up Session

Video (66 min.) : http://videocast.nih.gov/Summary.asp?File=16098

---------
Air date: Wednesday, September 08, 2010, 5:15:00 PM
Time displayed is Eastern Time, Washington DC Local
Category: Special
Description: This scientific conference has assembled an international group of scientists, physicians and epidemiologists to present and discuss, in a public forum, the latest XMRV studies on a range of topics including virus-host interactions, cell type tropism, mode of transmission, animal models, and diagnostic assay development.

This Web cast Q&A wrap-up session will touch on the latest developments in the field in order to evaluate the state of our knowledge, address controversies, and develop an understanding between experts that will help direct future research.

This workshop is co-sponsored by the NIH and will be organized by Virology Education.

For more information, visit
http://www.virology-education.com/index.cfm/t/Program/vid/1FFCB7B8-FB88-C1D2-92C420E3BCEB0FB0
Author: Stuart LeGrice and John Coffin; Virology Education
Runtime: 01:06:30
CIT File ID: 16098
CIT Live ID: 9582
Permanent link: http://videocast.nih.gov/launch.asp?16098

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac


#9 Zac

Zac

    Grande amico del forum

  • Amministratori
  • 2.827 messaggi
  • Gender:Male

Inviato 23 settembre 2010 - 22:30:28

September 23, 2010: 1st International Workshop on XMRV

Abstracts in Reviews in Antiviral Therapy & Infectious Diseases 46 page PDF format.

www.wpinstitute.org/news/news_current.html

Zac
Amministrazione

--------------------
"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
NO_CFS.gif

Le foto di Zac qui: PhotoZac





0 utente(i) stanno leggendo questa discussione

0 utenti, 0 ospiti, 0 utenti anonimi

Tutti i testi degli articoli e la veste grafica sono proprietà esclusiva di CFSItalia e ne è vietata la riproduzione, totale o parziale,

senza esplicita autorizzazione da parte degli amministratori.

Gli amministratori e moderatori non sono responsabili dei messaggi scritti dagli utenti sul forum. Il Forum ha carattere divulgativo e le informazioni contenute non devono sostituirsi alle visite, alle diagnosi e alle terapie mediche.