p>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.
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.
“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.
“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:
- by Megan Scudellari for The Scientist (April 1, 2011)
- by Amy Dockser Marcus for the Wall Street Journal (February 14, 2012)
- 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.
“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.
“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.
“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.