On the question of clarity of the diverse study results
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.
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.
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.
then -- an earlier question by
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.
I will skip many of the replies and jump to one of Judy Mikovits final comments.
Dr. Holmberg:-------------------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.
Those of us following developments with ME/CFS and Lyme Disease have to wonder if only CDC, Infectious Diseases Society of America and our Health Authorities around the World had listened over the last 30 years, instead of as is the case of Lyme Disease relying on just a handfull of people denying the existence of Chronic Lyme and with ME/CFS listening to the Psychobabble, whether science would have moved forward at a much quicker pace.
Instead it has been private funding pushing science forward and patients suffering the consequences of years of denial by our Health Authorities.