A report on the conference from InvestinME can be found here.
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.
A report on the conference from InvestinME can be found here.