Tuesday, June 5, 2012

InvestinME conference June 1, 2012

On Friday, June 1st, I was up early on a fine London day. It was the day of the 7th annual InvestinME conference. My hour-long early morning walk down through Green Park, St James Park, past the Horse Guards and along Birdcage Walk to the conference venue was exquisite. It gets me focused on what is to be a long day of intense listening and looking.

Some of the speakers at the InvestinME conference were familiar faces; some were not.  Several of the new ones came from fields outside of ME/CFS, an attempt by the organizers to draw connections to other areas of research.

The focus of this year’s conference was “Is ME/CFS an autoimmune illness?” The focus on autoimmunity stemmed from the work of Dr. Oystein Fluge and Dr. Olav Mella with Rituximab. Rituximab rules the day - although there were also other hopeful signs in research.

I will focus on a few of the presentations, knowing that full information will shortly be available in the form of a DVD of this conference. InvestinME sells this DVD at an affordable price and tries to get it as widely dispersed as possible.  They want to get this research out there.

Early in the day, Dr. Sonya Marshall-Gradisnik gave a fascinating talk entitled “Current Knowledge of Immunological Biomarkers in ME/CFS”. It focused on her work with NK cells. She works with a group at Bond University in Australia. Dr. Marshall-Gradisnik is a collaborator of Dr. Peterson with Simmaron. Her important research papers are listed here. Her lecture reiterated the litany: low NK cell numbers and function, low perforin, and a decrease in NK lysis in ME/CFS. Much of her study involves looking a t-regulatory cells and taking a further look at gene expression. She mentioned that some of her findings might point to autoimmune problems in ME/CFS. Further work is being done to come up with a marker for ME/CFS. She emphasized that her work is directed towards developing a combination of immunological markers.  She did say that NK cell function does not correlate with severity of illness. It occurred to me that Dr. Marshall-Gradisnik should be connected to Dr. Miriam Merad at Mt. Sinai ME/CFS Center, who also works in Immunology – and I made the suggestion.

Of the two Norwegians, Dr. Mella spoke first, outlining the Rituximab study published in fall of 2011. This study was first presented at the 2011 InvestinME conference, and Dr. Mella did us the favor of giving his presentation of the study again. This initial presentation gave Dr. Fluge the platform on which to build  - and to speak of more recent research.

Dr. Fluge gave new information on finding maintenance doses for patients on Rituximab, as the effects of the drug go away over time. They are running an open label maintenance trial for 28 patients, including patients from the first placebo group.  He showed a number of slides of different particulars in doing this. Most of this information continued the positive flow of the use of Rituximab in this patient population.  Dr. Fluge does not know why these patients relapse, but he wants to find out. They also want to find out why there is latency between treatment and improvement. A separate small pilot trial with five severely ill patients has encountered its own set of problems, many involving logistics of delivering the drug to this very sick patient group. Dr. Fluge also indicated that these patients might very well benefit from some sort of pretreatment prior to being given Rituximab. Dr. Fluge also mentioned a trial for non-responders with Etanercept.

The great hope of Dr. Fluge and Dr. Mella is that they will be funded for a larger trial of 140 patients and that they can gather more information.  Dr. Mella and Dr. Fluge will publish some studies after this summer. They have done a lot of experiments on immune measurements, autoimmunity and so forth. Some of the work shows negative finding and this too will add to the picture. Their general attitude is very upbeat and they are hopeful that further research will offer more answers.

They have no further proof that ME/CFS is an autoimmune illness. This supposition remains a theory and they are working hard to prove it – or to find out what other mechanisms might be driving the success of Rituximab. Another possibility, advanced by Dr. Kogelnik, is that the b-cells might be harboring EBV and that this viral load is lowered with Rituximab. Dr. Kogelnik is using Rituximab with antivirals, mainly Valcyte.

Dr. James Baraniuk has his own way of talking and it is very good – and amusing. Dr. Baraniuk returns from last year and this was good to see. He is another researcher with big ideas, and will only be restrained by diminished resources. Fortunately Dr. Baraniuk seems to be grinding along, doing what he does best – research. His research publications can be found here.  Dr. Baraniuk works on proteomics. His talk covered various aspects of the brain and migraines. He spoke of treatment with triptans. He spoke of “central sensitization” and emphasized that the dorsal horn of the spinal cord central is essential. He referred to areas where we find the ultimate lesions in ME/CFS and the loss of white matter in the brain stem. He spoke of a cascade- an inability to organize sensations. He stated that “default mode pathway” (zoning out) would play a part in this illness. Dr. Baraniuk works quietly away, and one suspects he has the capacity of hitting a homerun with his research.

Dr. Dan Peterson gave his usual fine talk. His objective was to point out the various research projects initiated in the last year. Certainly the Rituximab research is exciting - but there are other things going on, and Dr. Peterson listed them.  While emphasizing that many of the issues of the past remained unresolved – etiology, for instance – many other things are changing. He emphasized the increase in positive basic research and acknowledged that "a silver lining has perhaps emerged from the black cloud" of ME/CFS research of the past year. He pointed out the benefits and drawbacks of translational research concepts. He reviewed all new research projects in the last year, casting a great veil of optimism over the situation. The first study he described was the Lipkin XMRV study, mispronouncing Mikovits name several times in the process. This study's results are to be released June 30th. The results are a forgone conclusion.

Next Dr. Peterson mentioned the CFI’s pathogens discovery project, revealing the difficulties in gathering samples and information in this type of study. This was an enlightening moment to me, learning more about the nightmare of complex “designed” studies. The third study presented was the Bond-Simmaron NK cell pilot study, to which he is directly attached. The fourth was a CFIDS Association research projects. He went though all five projects of the “Research Institute without Walls”. The last project that he mentioned was the CASA project of the CDC.

In his overall thrust, Dr. Peterson is quite correct: this is a heady time for ME/CFS research.

I was surprised that he did not include the new ME/CFS research initiative at Mt. Sinai. This research center under the guidance of Dr. Derek Enlander includes Ila Singh, Miriam Merad and Eric Schadt.  For sure, Dr. Peterson is aware of this project, so it’s non-inclusion was a point of interest to me.

The big surprise for me in this conference day was Dr. Andreas Kogelnik.  Dr. Kogelnik’s name first surfaced in his working at Stanford with Dr. Jose Montoya on the Valcyte Roach trial. He holds degrees in medicine and in bioengineering/bioinformatics.  It seems that we don’t need to worry about this fellow’s academic qualifications.

A few years back, Dr. Kogelnik opened the Open Medicine Clinic in Mountain View, CA, and his clinic has collaborative relations with several local hospitals. At his clinic, Dr. Kogelnik is very aggressive in research and treatment - and he has a clear, though flexible, direction. At the moment he is doing a small pilot trial with Rituximab to see if he can get positive results. He is also using Valcyte and has plans for other studies. He noted the recent published trial on Ampligen and hopes that the CDC might be turning the corner with this additional treatment.

The first thing that struck me about Dr. Kogelnik is that he is very young for an ME/CFS clinician. Most of these personalities are older folk, so it is good to see a younger clinician/researcher being so active, confident and aggressive. He is what you could call a welcome new face. He does not seem to be inhibited by the larger problems in the ME/CFS world and is intent on keeping his eye on the ball and moving forward. Much is expected of him and let us hope for the best.

Dr. Kogelnik generates a huge sense of optimism. He believes that the “mainstream is getting interested” in ME/CFS research. He thinks that the biomedical and treatment possibilities are reaching a critical mass. This was the general feeling from a variety of participants in this conference. It is certainly true that there is, emerging from the downfall of XMRV, a high and broad level of research. Whether it will disappear into the pit of all previous disconnected, discombobulated research, we will see in time.

Perhaps the most intuitive thing that Dr. Kogelnik has done is to collaborate with Dr. Peterson. These two have formed a close and warm collaboration. Drawing on the resources of an older, experienced clinician/researcher is a natural and savvy move. It also indicates that Dr. Kogelnik is not overly hubristic, and has enough sense to learn critical matters from another person. I am sure it has great benefit to Dr. Peterson also, who must, about this time, be looking for some "continuity into the future" for his work and experience.

In fact, the entire direction of the Open Medicine clinic is towards outreach and collaboration. Their attitude is inclusive; they want to bring people in. The clinic wants to do studies and accumulate data to share with other institutions. (Somehow this all sounds familiar.) Dr. Kogelnik gives every indication that he will carry through with this. With collaboration and inclusion in mind, Dr. Kogelnik is sponsoring an invitation-only research meeting in NYC in June. While the agenda of this meeting is not published, the subjects can easily be nosed out.

A few more thoughts:
It is always surprising that so few Americans go to this conference, and/or that so little attention is given to InvestinME in the United States. It makes no sense to me. This conference is the place to be if you want to learn what is happening in biomedical research into this illness.

Two other ME/CFS clinician/physicians have indicated to me privately that they both, and separately, have come to understand the etiology of this illness. I present this to suggest that there are additional things happening. Hopefully there will be publications.  

The most interesting thing for me about these conferences is meeting patients and patient advocates. Many of both are in attendance at these InvestinME conferences and they play a big part in its success. The patients and advocates have a reality about them that is very special, and to come into contact with them is like an epiphany for me.  They harbor certain undiluted truths, and, frankly, too little attention is awarded to their experience and knowledge. Often at these conferences, the clinician or researcher seems to be in ascendance; they are the “Important Personages”, and often they have difficulty “dropping the mantle”. But I know better. It has long been my feeling that many ME/CFS physicians have no real idea about this illness and its devastations. Often they remain in a self-protected mode, hunkered down in their little groups. (Certainly there are exceptions. I saw Dr. Kenny De Meirleir today. He came in, rolling his little bag straight from a trip to Australia, Later this week he is off to Norway, where, among other things, he will visit severely ill patients.)

In contrast to this is the reality of patients and advocates, who are at ground zero of this illness - and it shows in their grace, humility, intelligence and shared values, acquired through living very close with this horrible illness. Each is inching, often on their own, towards betterment. It is a privilege to meet these people at this conference, where their attendance is encouraged and their participation is critical.

In the future I would like to see a conference devoted entirely to treatment, attended by clinician and clinician/researchers (no pure researchers). I would like to see a large group of physicians wrestle together over the efficacy of present treatments, of which there are many. There is great need for a general treatment protocol, particularly for newly diagnosed patients. Such a conference could also focus on pilot studies of treatments that might be useful and form the basis for the accumulation of data. I believe there is a great amount of clinical experience that could make a meaningful consolidation of treatment options. Of course, egos would have to be checked at the door – but is this possible? The NIH, of course, should have done this many years ago, but they have declared that they are “indifferent” to the fate of ME/CFS patients. They have failed this patient community, so it is going to depend on private resources to move forward with treatment.

A report on the conference from InvestinME can be found here


  1. Loved your opening remarks Chris. As someone homebound/bedbound I enjoyed parts of that walk with you.

    Thanks for taking the time to present a review of this important conference to the community. You always seem to bring meat and potatoes to the table. A lot to look forward to for those who will make it through another year.

  2. Lovely to hear of your morning walk through London parks and thank you for the detailed report on this year's conference.

    It's a privilege to read your thoughts and observations.

  3. Thank you for this overview, Chris. It's always refreshing to get your first-hand perspective on a conference like this.

    I agree that it would be great to get the leading ME/CFS clinicians together in a conference to discuss cutting-edge treatments. I truly hope this will happen. It's sorely needed.

    1. We need scientists. It is beyond a joke that these clinicians are using the Fukuda criteria and then relying of self-report questionnaires.

  4. Regarding the statement that "Two other ME/CFS clinician/physicians have indicated to me privately that they both, and separately, have come to understand the etiology of this illness", I don't think there will be 'an etiology' to 'this illness'. If ME/CFS is a disease of subgroups then it seems likely there would only be 'etiologies' to 'these illnesses' and looking for one singular etiology is doomed to failure. That is why no reliable biomarkers or treatments have emerged thus far.

    As an example, say you had two groups participating in a research study, Group A and Group B, each with 50 patients for 100 patients total. If 35 of 50 in Group A had a particular lab abnormality/response to treatment and 40 of 50 in Group B had a different lab abnormality/response to treatment, then that would be 70% of Group A and 80% of Group B (35/50 and 40/50), which are pretty good numbers. However if the two groups are not seperated then you end up with 35% and 40% respectively (35/100 and 40/100), which is not nearly as good and what has likely been happening in ME/CFS research for quite some time now. It's not that 'ME/CFS is different for everybody', it's just that different subgroups are being studied together. For people in the same subgroup the illness is the same.

    Such a finding was most recently suggested by the recent Light/Bateman study which found that 71% of the participants were in one subgroup and 29% were in another subgroup, with the smaller subgroup having 71% of the POTS patients in the study. http://www.research1st.com/2011/06/02/exercise-challenge-reveals-potential-cfs-biomarkers/

    Such a finding is also suggested by the Rituximab results, which found that not only did 1/3 of patients not respond to the drug at all but also that some patients respond early, within 6 weeks, while other take 6-8 months to respond. This could mean that there are 3 subgroups, the non-responders in one, the early responders in another and the late responders in the third.

    The issue of subtypes also occurs in multiple sclerosis. Recent research reported that there is one type of MS characterized by Th1 and which responds to interferon beta and another type of MS which in characterized by Th17 and is exacerbated by interferon beta. If similar findings also occured in ME/CFS it would explain why drugs that work for some don't do anything for others and make others still worse, which is notorious for occuring in ME/CFS.

    Whoever cracks the nut of subgroups is probably going to move the field forward by leaps and bounds and it is only then that the true pathology of ME/CFS will be unravelled.

    1. Excuse me, 'true pathologies' will be revealed.

  5. Thank you again for this more narrative report! Looking forward to recieve the DVD, so thank you for this preview!
    There are some realy exciting things going on!


  6. A great write up Chris. It's really positive to see that interest in 'CFS' is now at the highest we have ever seen it. I wanted to add one thing if I may though.

    And this is that 'XMRV' was never detected in people with CFS in Lombardi et al, 2009. It was MLV's,(polytropic) but these MLV sequences are not sequenced or cloned. Without this, one cannot 'prove' much other than further the science.

    That's what Mikovits was about to do before the WPI's actions (apparently) got her arrested. The type of gamma retrovirus the WPI found in 2009 are the same (without Silverman's VP62 'X' contaminant never found in a human), as the type Alter found in 2010 and the type Maureen Hanson and David Bell found. This group and have just published on 'CFS' this month and its a positive paper.

    XMRV in 'CFS' is most certainly a Dodo I agree, but polytropic MRV research has only just started. Do read this paper if you haven't seen it. We can see in the future that tissue biopsies will be required for 'CFS'. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357399/

    Understanding this, one can see why a B cell depletion therapy would work in infected 'CFS' patients, as it's known retroviruses infect B cells (bone marrow). Also notice that when Rituximab is stopped, the symptoms return. This proves an on-going infection. Retroviruses cause autoimmune diseases.

    To the poster who said Ritixumab didn't work on 1/3 of patients. This is normal when using autoimmune drugs such as this. 1/3 patients who take this class of drug aren't helped with Rituximab in other illnesses (arthritis/Lupus etc). Also the cohort Fluge & Mella used aren't all severe grade 'CFS' patients like in the WPI paper of 2009. They include Fukuda (CDC) four symptoms and chronic fatigue - 'CFS'. Thus any reason can be why these folk are sick, and of course, they won't all have ME.

    Now we have early data suggesting we know that the action of'CFS' symptoms have been discovered by Fluge & Mella (B Cells) we must find out the CAUSE of WHY these B Cells make patients so ill.

    Simply settling for 'it's an autoimmune disease' and putting patients on medications to block symptoms is not enough. Especially when we know there is so much to look at with polytropic gamma retroviruses (not XMRV the synthetic virus), human gamma poly's found in the blood cells of people with 'CFS'.

    So yes I agree, research is looking very exciting at the moment and I am grateful to all the scientists, doctors and bloggers who keep people informed.

    I saw the other day on an official University of Pittsburgh (department of Urology) blog that other scientists out there have positive gamma retrovirus papers and are too scared to publish because of the ongoing bio-politics!


    I think 2012 will be interesting, and 2013 even more so.

    Thanks again for your blog Chris and keeping us all motivated and full of hope. As we certainly do all need hope that the climate will change to more favorable weather.

  7. Chris, thank you so much for covering this conference.
    I noticed you said Mella and Fluge have some negative findings. This implies they also found something positive. Did they elaborate on those positive findings or are they keeping quiet until their research is published?

  8. thanks for this, chris.

    hmm. why would peterson purposefully mispronounce mikovits' name?

    1. I am not a fan of Peterson. What more can be said at this time.

      The evidence only supports that ME patients are infected with MRVs. The same goes for prostate cancer patients.

      None of these viruses are XMRV.

      The "Lipkin" study is not a replication study.

      There is no evidence that a recombinant virus was created in the 90s.

      The 22Rv1 cells have not been shown to contain the XMRV.

      Patients deserve science not opinion.

  9. Maureen Hanson found MRVs in Bells Canadian criteria patients using clinically validated assays. She could find no virus in Levine's Fukuda patients or with assays that were not clinically validated.

    It is simple. They have to clinically validate their assays, which so far they NONE of the negative studies have done and they need to use the Canadian criteria.

    So what is Lipkin doing using a criteria in the NIH/Fauci study that isn't the Canadian criteria? The paper is already invalid.