By K. Kimberly McCleary, President & CEO
For weeks we have used construction metaphors to describe the preparations for today’s announcements. With those preparations behind us, we can finally share the news about the latest set of additions to our research program. So, what have we constructed?
We’re calling it a research institute without walls. No nails, no Sheetrock, no 2×4 lumber required. For this ground breaking, there is no dirt to shovel, no ribbon to cut. The projects we will link under our “roof” are preparing to start. In fact, a few of them are already under way and the SolveCFS BioBank infrastructure at the “institute’s” core has already enrolled 458 participants. So, while we’re not really breaking ground, we believe our approach merits use of the term “groundbreaking.” Here’s why.
All the projects we have greenlighted are focused on advancing effective treatment, including the need for better ways to diagnose and subtype CFS. We know of no other set of projects launched simultaneously with this goal in mind.
All of the projects will be linked through us and to the SolveCFS BioBank. Three projects will recruit subjects at their sites and new study participants will have the opportunity to enroll in the BioBank. Two of the projects will test BioBank samples already in inventory. One of the projects will utilize the extensive clinical data collected from BioBank participants. Several projects will utilize powerful “big data” computational tools to mine the medical literature and other sources, including the BioBank. Never before has one CFS resource been maximized so fully. And it will become more valuable as these studies progress and add data to what we’ve already collected.
Five of the projects were selected from the 26 applications to our April 2011 Request for Applications; these five ranked at the top for scientific and strategic merit. These are described in our press release and in more detail below. They will be coordinated individually and as a group by our scientific director, Dr. Suzanne Vernon. As we demonstrated with our 2009-2010 grants, this collaboration and coordination strengthened the individual studies and facilitated new partnerships.
Dr. Dane Cook’s project is a perfect illustration of the synergy we set out to create. Dr. Cook was a collaborator on our grant to Dr. Sanjay Shukla; he performed the exercise testing studies on subjects enrolled in Dr. Shukla’s microbiome study. Through this collaboration, he was introduced to Drs. Kathy and Alan Light (University of Utah) and followed closely their studies of post-exercise blood markers. He was also introduced to Dr. Gordon Broderick (University of Alberta) and his powerful data analysis techniques. Dr. Cook’s project funded in this round teams his group at University of Wisconsin-Madison with the Lights and Dr. Broderick, providing a valuable validation effort using their techniques, and enhanced by the brain imaging work for which Dr. Cook has established a reputation. That’s seismic, ground-shaking stuff, especially with such a modest award.
We have been able to engage the interest of top experts, working at the leading edge of multiple scientific disciplines. Imaging. Post-exercise biomarkers. Big data analysis. Drug repurposing. Epigenetics. Metagenomics. Couple this with clinical investigators relying on solid physiology and years of experience evaluating CFS patients and, again, it’s revolutionary.
So, these are just a few reasons why — even without a shovel or a backhoe — we’re referring to this set of projects as groundbreaking. We hope you will too.
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Dane Cook, Ph.D., of the University of Wisconsin-Madison
Dr. Cook has teamed with Alan Light of the University of Utah and Gordon Broderick of the University of Alberta to link information gathered from exercise testing, brain imaging and gene expression markers in the blood to understand post-exertional relapse, a hallmark feature of CFS. This project will attempt to validate blood and brain markers independently identified by these investigators in earlier studies.
Project Overview for Dr. Cook’s Study: Post-exertion Malaise in CFS/ME: Brain, inflammation and behavioral interactions (URL: http://bit.ly/2012-cook)
“The investigators associated with this project are grateful for CFIDS committment to advancing the science of CFS through interdisciplinary and collaborative research. This study marks one of the first attempts to examine the interactions between the brain, the immune system and patient symptoms – a necessary approach to the study of this complex illness.” – Dane Cook, Ph.D.
Spyros Deftereos, M.D., of Biovista, Charlottesville, Vir.
Drug repurposing is the process of deploying existing drugs for therapeutic uses other than the ones for which they were originally designed. This process cuts the cost and timeline to identify new therapies. Under this grant, Biovista will use its proprietary COSS™ Drug Repurposing platform to to systematically identify non-obvious drug candidates to treat CFS.
Project Overview for Dr. Deftereos’ Study: Identification of Drug Repurposing Opportunities for the Treatment of CFS (URL: http://bit.ly/2012-biovista)
“We believe in the power of systematically exploring all drugs and mechanisms for their potential against any disease. We have used this idea as the driving force to create a technologic capability, COSS, that maps and ranks all drugs versus all diseases, side effects and molecular targets of disease, and vice versa.
“We are very happy to be working with the CFIDS Association because we believe the challenges faced by a complex disease can best be met initially by a combination of approaches, which include systematic repositioning. An often unrecognized virtue of repositioning done right is the possibility to uncover unexpected biology. This means that because drugs work in a variety of ways, we can explore the ‘unexpectedness’ in a way that sheds new light on a disease and can re-invigorate the space. There are excellent examples, of this, including cancer drugs working in Alzheimer’s or arthritis, NSAIDs in Parkinson’s and others.” — Spyros Deftereos, M.D.
Learn more about drug repurposing:
- “Teaching Old Drugs New Tricks,” by Megan Scudellari for The Scientist (April 1, 2011)
- “Dilemma: When 1 Drug Treats 2 Diseases,” by Amy Dockser Marcus for the Wall Street Journal (February 14, 2012)
- “How To Successfully Repurpose A Drug,” by Amy Dockser Marcus for the Wall Street Journal (February 14, 2012)
Patrick McGowan, Ph.D., of the University of Toronto Scarborough
There is substantial evidence of environmental influences on CFS symptoms and severity, affecting the function of a number of immune system genes. Mechanisms that alter the function of genes in a long-term manner without changing the DNA sequence are called “epigenetic.” Using samples collected through the SolveCFS BioBank, McGowan will conduct a state-of-the-art investigation of epigenetic marks across the genome to detect changes in immune cells and their relationship to CFS symptoms. This study may uncover novel biomarkers to help diagnose CFS and assess the outcomes of therapeutic interventions.
Project Overview for Dr. McGowan’s Study: Epigenetic Alterations of Glucocorticoid Signaling Pathways in CFS (URL: http://bit.ly/2012-mcgowan)
“The pace of innovation in epigenetics has been rapidly accelerating over the last few years, and now stands to have a major impact on our understanding of complex diseases like CFS. I am thrilled that the CFIDS Association of America is funding this cutting-edge research into the biology of CFS.” — Patrick McGowan, Ph.D.
Learn more about epigenetics:
- “Why DNA Isn’t Your Destiny,” by John Cloud for TIME magazine (January 6, 2010)
- “Epigenetics – A Primer,” by Stefan Kubicek for The Scientist (March 1, 2011)
Marvin S. Medow, Ph.D., of New York Medical College
This study will extend earlier work supported by the Association that shows orthostatic challenge, such as prolonged upright posture, leads to problems with memory, concentration and information processing in people with CFS. First, Medow’s team will measure brain blood flow during a head upright tilt test while testing cognitive ability to establish baseline measurements. Subjects will return for additional studies to test three interventions selected for their potential to increase brain blood flow. These studies will inform potential therapies directed towards reducing neurocognitive impairment, or brain fog, experienced by many people with CFS.
Project Overview for Dr. Medow’s Study: Understanding Brain Fog in CFS: Reduced Cerebral Blood Flow Impairs Cognition (URL: http://bit.ly/2012-medow)
“It’s been my honor and privilege to work with the professionals at the CFIDS Association during the past several years. Their continued support of our research, and that of others, will provide answers to important questions about chronic fatigue syndrome.” — Marvin S. Medow, Ph.D.
Learn more about orthostatic intolerance:
- “The Ins and Outs of OI,” by Kim McCleary for Research1st (June 19, 2011)
- “Is It Anxiety or OI?” by Kim McCleary for Research1st (June 21, 2011)
- “Going with the Flow: Blood Flow, That Is,” webinar by Marvin Medow, Ph.D. (March 10, 2010)
Peter Rowe, M.D., of Johns Hopkins Children’s Center in Baltimore, Md.
Working with CFS patients for nearly two decades, Dr. Rowe has observed that simple movements like a straight leg lift can trigger fatigue and brain fog in CFS patients. Dr. Rowe’s group hypothesizes that the underlying mechanism is similar to fibromyalgia pain, where nerves become extra sensitive to stimulation, a process known as central sensitization. His work will be among the first to explore the possible link between fatigue, cognition and central sensitization. The results are expected to identify a subset of patients who will benefit from a different therapeutic approach.
Project Overview for Dr. Rowe’s Study: Neuromuscular Strain in CFS (URL: http://bit.ly/2012-rowe)
“My physical therapist colleague Rick Violand first introduced me to the concept of neuromuscular or neurodynamic strain, and we’ve been interested for years in how it appears to play a role in CFS symptoms. Now, in collaboration with Kevin Fontaine and Kristi Mizelle, we’ve put together some methods for studying it formally. We’re excited to be able to get the ideas to this stage, and expect some important insights and practical implications from this project, especially for treating those with CFS.” — Peter Rowe, M.D.
More info about two new projects approved through the SolveCFS BioBank being conducted by Dr. Eric Delwart (Blood Systems Research Institute) and Dr. Leonard Jason (DePaul University) and the LogosOmix “biomarker hit list” project will follow.
K. Kimberly McCleary has served as the Association’s chief staff executive since 1991.
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I’m so excited to see these approaches! There are so many new big-picture technologies available to start interrogating the bodies of PWCs, like genomics, proteomics, metabolomics, etc. I’m especially excited to to see the drug repurposing. Not only can one not predict which processes will be involved in certain illnesses, most drugs are surprisingly nonspecific. That can sometimes be unfortunate with regard to side effects, but the flip side is that many drugs target unknown processes and thus might be effective for treating diseases totally different from those for which they were designed. Way to go CFIDS association for promoting innovative research!
It is fabulous to see for ourselves the advancements we have to look forward to with these highly respected medical staffers who are dedicated to finding causes and cures for those of us who suffer with NEIDS. Thank you for making this information available to us. Thank you Suzanne Vernon for continuing the fight for us. May God bless your research to gain insights into the complexities of our diseases.
Hi CAA,
I have a question. Wouldn’t it be a good idea for the CAA to require that investigators who obtain CAA grants send in lots of extra patient samples to the CAA Biobank, or is the CAA already doing this? If ME/CFS truly is a disease with/of subtypes, as is suspected, then matching up new findings with old findings will be paramount to fleshing out the abnormalities and/or biomarkers for these subtypes.
For example in the newly CAA-funded study by Patrick O. McGowan, “McGowan’s hypothesis is that there is an epigenetic mechanism in CFS that disrupts glucocorticoid signaling in white blood cells called lymphocytes”. (1)
However if McGowan’s hypothesis is only confirmed in a proportion of patients, ie one potential subset/subtype of patient, then what’s the point? Won’t it be yet another study where a percentage of patients have XYZ wrong with them but since it’s not 100% of the cohort then it’s off to the next hypothesis? But if McGowan was able to correlate the patients who had the lymphocyte abnormality in his study (should any such abnormality be found) with, say, patients who were part of either of the subtypes reported in the Lights’ gene expression study, either the 29% in the a-2A decrease subgroup or the 71% in the everythingandthekitchensink subgroup, then wouldn’t that be a much bigger deal? So would it not be a good idea for the CAA to make a priority of archiving samples taken from patients from previous CAA-funded studies and/or making a priority of obtaining continual samples from patients in such studies so that any putative abnormalities reported could be matched up between different studies?
Thanks a bunch to the CAA and good luck with the research program. Now all we need is for the NIH to kick down some funding for a collaborative research program with walls and we’ll be all set! It’s so weird to think that $7.5 million (5 CoE’s at $1.5 million a piece annually) is so little to the NIH but would be so huge to us!
1. http://medicalxpress.com/news/2012-02-environmental-triggers-gene-function-chronic.html
First, to all who have posted here — many thanks for your inspiring words and the hope you have shared with us.
John, thanks for your question. I’ve seen similar points made elsewhere, so I’m glad to have the opportunity to respond. What you’ve outlined is exactly what we’re working toward. It’s why we’ve put the SolveCFS BioBank at the hub of the wheel.
We have required the studies recruiting their own subjects to encourage their subjects to enroll in the BioBank and we’re working through the various regulatory issues with Institutional Review Boards (IRBs), etc. to make that possible. We can’t “require” BioBank enrollment of every subject because of the ethical issues that would create. The BioBank is intentionally a voluntary, participatory construct. We anticipate a high degree of motivation among the participants in the clinical site studies to be involved in as much research as possible.
Also, it’s important to keep in mind that the studies we funded came about as the result of a “sealed bid” process. In other words, the investigators have to propose research based on what resources and collaborations they have access to. It’s unlikely Patrick McGowan would have known to contact Dane Cook before we made (so far only email) introductions when the awards were announced. It’s like Dane Cook’s study for this round, involving collaborations with the Lights and Gordon Broderick, wasn’t one of the applications submitted in 2008 because Dane didn’t know about the work the Lights were doing or the way in which Gordon could aggregate and analyze complex data sets. It’s a lot to expect that someone working in epigenetics would know about post-exercise blood biomarkers being developed for a condition he had not previously studied. We have some ethical obligations to maintain the integrity of the process and there are limitations to the match-making we can do in the midst of the process. That said, like we did with grantees in 2009-2010, we will be bringing the funded PIs together regularly and expect to see the same types of collaborations borne as we did the from the last round. The study you’ve outlined would make a tremendous RO1 application to NIH and would require (financial) resources on that scale to do properly. Again, it’s exactly what we’re working toward. We’ll need not only more funding, but also more sophisticated funding mechanisms and processes to accomplish it.
One other small thing to keep in mind — there is a limit to the amount of blood sample that can be collected at any one time point and within a certain amount of time (for obvious health reasons, and especially when studying a condition where low blood volume may be a factor). While it’s tempting to think that we could collect multiple samples for immediate study and long-term storage in the course of these studies, patient safety must be safeguarded. That’s why IRBs exist and they do look at the protocols to ensure that there are minimal risks to the patients involved in these studies. Also, the processing requirements for samples to be used in different studies differ greatly and it is not as easy as it may look to sync up how the samples might need to be collected, processed, stored and transported to maintain their characteristics for the end user. We are fortunate that the very samples Patrick McGowan needs for his study were available within our existing inventory, otherwise this study — a first-ever epigenetic study for CFS — would not have been possible under our budget caps.
Hope that answers your questions and others I’ve seen posted elsewhere!
Thanks to everyone for tremendous interest and engagement!
One wall that still needs to be torn down is the belief among many members of CFS/ME groups that men and women whom have GWI(Gulf War Illness)that their illness is a complete and separate illness.
Some of these grants look like very good ideas to this non-science person, especially the drug search project. I do really wish that CAA would go that extra necessary (imo) step and use CCC and ICC in their Biobank. It is such a simple step and would momentously improve the science. CAA does include PER/PEM/PENE as a mandatory criterion, to their credit. But one has to wonder why they are so invested in Fukuda and other CDC nonsense.
Hi Justin,
Thanks for giving me the opportunity to clarify this again. The BioBank registry seeks to enroll the broadest group of participants possible, from the most severe end of the illness spectrum to healthy controls with no current or past significant medical history. When we approve a study for use of BioBank resources — whether clinical information or biological samples, we can provide the investigator with subjects (cases and controls) who match the study criteria, whether they wish to study individuals with acute onset who meet Canadian criteria or all degrees of illness severity with documented orthostatic intolerance. We also enroll contact controls and people who consider themselves recovered. All of these people may serve an important role in better understanding CFS. Because we are partners with the investigators who are approved to use BioBank resources, we can help guide the selection of participants and samples to hone on the ideal population to study. To limit the population enrolled in the BioBank would limit what we can learn.
An example of this is that Dr. Delwart’s metagenomics study will use samples collected from a highly screened group of participants who carry a diagnosis made by CFS expert physicians, had an acute onset of their illness, have post-exertional relapse as an ongoing symptom and meet both Canadian and 94 (Fukuda) criteria. Depending on what he finds, it will be possible to study a different set of patients, perhaps those with gradual onset or who meet only Fukuda criteria, to see if the same results hold for that group.
I was diagnosed with CFIDS and FMS in 1992 and 98. In 2010 I was tested and it showed that I have chronic, late-stage Lyme Disease. Could Lyme Disease research be included in your work? Also, could I take part in the bio-bank?
I have been registered with the BioBank for a couple of years and have never been asked for so much as a blood sample. Why?
Dear Perry,
We are grateful for your participation in the BioBank. To make sure that the biological samples collected from our participants will meet the needs of specific research studies, we only collect samples to meet specific requirements. As the news about this unique research resource reaches qualified investigators, we hope to have need for more blood and tissue samples and will contact enrolled participants as those needs dictate. Thanks for asking this important question and for being on standby for the next collection!
How do I obtain any support for my daughter who has CFS and can not work a full time job on a regular bases? What can I do to help her? What hope is there for her for her future? Are there any grants that financially assist medical expenses that are not normally covered for someone like this?
With the success of the Ritimax trials, it seems that more focus on immune issues would be important. While all this (mostly neurological and brain/cognitive focused) research seems great, my only regret is that there are no immune focused studies here. Especially since I am a fairly moderate to severe sufferer without pain or sleep issues and almost no brain fog.
What sites & search terms would you recommend for somebody with autonomic dysfunction (and no money – it is gone) who is seeking medical studies for Dx and possible treatment?
Hi PG,
Please read these two articles and links from them to other resources:
“The Ins & Outs of OI”: http://www.research1st.com/2011/06/19/the-outs-and-ins-of-oi/
“Dysfunction Junction: The ANS & CFS”: http://www.research1st.com/2012/03/05/ans-dysfunction/
Hope these resources are helpful to you.
I’m trying too sign up for your
Newsletter/unable to do so???
ALSO TRYING TO REACH
COCO CRUM….
can u help ?
Hi Ellen,
We’ll take care of signing you up for Research1st News on our end, no worries! We’ll also pass your email address to Coco Crum. Thanks for participating on Research1st.
I would like to be added to your news Letter list. 4 years ago I came down with CFS. I think every test was run to start ruling out msny thing. For 18 months I with though this with no help. Then as quick a sit came it left. That is until two months ago. I want to know more! I have copiers of all the test and durg that I was treated with.
Thank you,
Linda
Thanks, Linda. We’ve added you to our mailing list for Research1st News, our monthly update on research, policy and events. We invite anyone to subscribe to the free monthly update: http://bit.ly/R1stNews-signup