Association-Funded Researchers Making Headway

By Suzanne Vernon, PhD, Scientific Director

In March 2008, the Solve ME/CFS Initiative issued a funding opportunity announcement for studies of biomarkers for early detection, objective diagnosis and treatment of CFS. Following a thorough peer-review process and evaluation of the top proposals’ strategic merits, funding for six research studies was announced in November 2008. Four studies got under way by March 2009 and the other two launched in June 2009. All six teams of investigators have hit the ground running. Here are some current highlights:

Drs. Kathy and Alan Light and their University of Utah research team are looking for objective diagnostic markers of CFS. Earlier this summer, the Light team published new findings in the Journal of Pain describing blood-based markers that appear linked to symptoms of fatigue and pain in CFS. They are detecting receptors specific to metabolites created by the muscles during a moderate exercise challenge. What is notable is that the markers are not present when CFS subjects are at rest. However, after moderate exercise on a stationary bicycle, the expression of these markers on blood cells increases dramatically in CFS subjects, but not in healthy controls or patients with multiple sclerosis (another condition with substantial pain and fatigue) who exercise the very same way. This means that – so far – these markers appear to detect the post-exertion fatigue that is the hallmark of CFS. A diagram illustrating the difference in the markers appeared on the cover of the October 2009 issue of the Journal of Pain. The Light team is testing more CFS subjects and other disease control groups to determine just how specific these markers are to CFS. If it pans out, this may be the first objective diagnostic blood test for the hallmark symptom of post-exertion fatigue in CFS.

Dr. Dikoma Shungu at Weill Cornell Medical College and his collaborators continue to examine brain metabolism in CFS. In 2009, Shungu and his team published a paper in aprestigious imaging journal, NMR in Biomedicine, describing increased lactate levels in the brain cerebrospinal fluid of CFS patients. Elevated brain lactate is an indication of metabolic disturbance in CFS. It is notable that this was not found in the healthy control and disease control (generalized anxiety disorder) comparison groups tested. With their current award from the Solve ME/CFS Initiative, Shungu has extended the study to include more CFS subjects and a major depressive disorder disease control group. An exciting aspect of this study is that these subjects will also participate in Dr. Marvin Medow’s study which examines blood flow (see below). This pair of investigative teams has developed a model that is based on infection causing inflammation and oxidative stress that alters blood flow and increases brain lactate. Elevated lactate can be detected by MRS, a non-invasive imaging test. This could be an important approach to detect CFS early in the course of illness, important since the earlier CFS is detected and diagnosed, the greater the chance of effective intervention.

Dr. Marvin Medow and his team at New York Medical College study postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance associated with signs and symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive deficits. Many young people with CFS also have POTS, and at least half of adults with CFS have POTS. Medow studies whether these POTS symptoms are due to reduced brain blood flow. He and his team published a paper in The American Journal of Physiology – Heart and Circulatory Physiology in August 2009 describing decreased brain blood flow and altered regulation of blood flow by the brain in POTS patients. Medow and his team continue to study why blood flow is altered in CFS and are examining chemicals in the body that cause oxidative stress and molecules that affect the function of blood vessels. Subjects that participate in the Medow study also participate in the Shungu study described above. This will allow the Medow findings on blood flow mechanisms in the body to be related to the blood flow and metabolic alterations that Shungu is finding in the brain of CFS patients. This type of integrated study of blood flow alterations has the potential to improve CFS treatment.

Dr. Gordon Broderick of the University of Alberta has been working with colleagues at Northwestern University and University of Illinois-Chicago to understand how Epstein-Barr virus (EBV) can trigger CFS following infectious mononucleosis (also known as mono or “kissing disease”). Broderick is a systems biologist who uses sophisticated mathematical approaches and powerful computers to construct models of CFS based on actual clinical and laboratory data. He has published several papers over the past year that model how the brain, endocrine system, and immune system are altered in people with CFS. A figure from one of his 2009 papers made the cover of the journal Genomics. When he is not in his laboratory, Broderick teaches medical students about computational biology and uses examples of CFS in many of his lectures. Broderick recruited five medical students to conduct research in his group with the objective of raising awareness of CFS and CFS research among tomorrow’s clinicians. In addition to getting exposure in the media, the medical students publish their work in the peer-reviewed literature.

Dr. Sanjay Shukla of the Marshfield Clinic Research Foundation will study gut microbes in CFS. We now know that humans require the right kind and the right balance of microbes in our intestines to stay healthy. Shukla hypothesizes that people with CFS do not have the right kind and balance of microbes and that exertion causes the microbes to leak across the intestine causing inflammation and metabolic disturbance. He has assembled a team of experts in internal medicine, exercise physiology and bacterial phylogeny to assist him in this innovative study. The team began enrolling patients and controls in July. They will collect blood and stool samples before and after an exercise challenge to study how exertion affects gut function and ecology. Stay tuned to what are certain to be interesting and important results that could impact the diagnosis and treatment of CFS.

Professor Bud Mishra and his bioinformatics team at New York University will use computer software they developed to identify subtypes and possible causes of CFS. Mishra and his team are compiling medical records from hundreds of well-characterized CFS patients to accomplish this. Once the medical records have been converted to an electronic form and then “read” and interpreted by the computer, a team of human experts will evaluate how well the computer has interpreted the information. Sound futuristic? Perhaps, but the reality is that using computers to process large records and search for patterns is a smart application of “artificial intelligence.” Many people with CFS have huge binders for their medical records. Mishra’s team is essentially searching medical records from hundreds of CFS patients to identify CFS subtypes and causes. Think of this project as a highly specific application of Google-like technology that will identify new information and translate it for use in clinical settings.

Suzanne Vernon, PhD, is the Association’s scientific director. She has nearly two decades of experience as a microbiologist

January 6, 2010