The first program funded by the Association was its research grant program. Since 1987 the Association has provided nearly $5 million in direct support of CFS research studies, has hosted scientific symposia and has cosponsored meetings to identify promising areas of investigation.

During the 2006-2007 funding cycle, five CFS research projects totaling $288,900 in support were awarded, as described below. The current purpose of the CFIDS Association’s research program is to accelerate progress toward accurate diagnosis and effective treatment of CFS by directly supporting research studies, facilitating collaboration among investigators and pursuing increased investment in CFS research by public, private and commercial institutions. 

The CFIDS Association of America regularly issues funding announcements as part of its research grants program. Its most recent Request for Applications was issued on March 3, 2008. This Request for Applications (RFA) solicits research proposals that will advance the discovery of biomarkers and methods for early detection, objective diagnosis and effective treatment of CFS. For more information about this funding opportunity, please visit http://www.cfids.org/profresources/2008rfa.asp. 

For more information on the Research Grants Program contact the Research Grants Officer. 

2006-2007 Awarded Research Grants

Studies on the Etiology of Chronic Fatigue Syndrome

Investigator: Ronald Glaser, PhD, Ohio State University, Columbus, Ohio
Budget: $48,950

The Epstein-Barr virus (EBV) has been linked to CFS for many years along with several other viruses, such as human herpesvirus 6 (HHV-6). In spite of the fact that at least one subgroup of CFS patients, known as acute onset patients, have symptoms commonly associated with a viral infection, there are no consistent studies that establish EBV or any other candidate virus with CFS. It is still not clear why it has been so difficult to identify a virus (or viruses) in CFS patient. One factor that makes it difficult to identify a single virus, like EBV as the cause of CFS, is that virtually everyone is infected with EBV by the time they reach middle age and, thus, have antibodies to the virus even if they are in perfectly good health; we all have a repertoire of antibodies that we have because of previous exposure to viruses.

Dr. Glaser’s group is exploring new approaches to try to understand how a virus, like EBV, might be involved with CFS. We have found evidence that some EBV proteins or “pieces” of the virus can, by themselves, produce abnormal changes in immune cells and that these changes might cause CFS in acute onset patients. Trying to identify these proteins or antibodies to the proteins (as part of the diagnostic workup) is complicated and not performed by routine analysis. In addition to measuring antibody levels to EBV-encoded proteins, we will also use a proteomics approach to determine if we can identify any viral or unusual serum protein patterns in serum samples obtained from CFS patients and control subjects as well as serum obtained from patients with acute infectious mononucleosis (IM), which is caused by EBV, and serum from IM patients 1, 2 and 6 months following diagnosis of IM. Blinded and coded serum from the initial and 6-month visit from patients who self-reported recovery by the 6-month visit and patients who did not recover will be characterized. These studies will allow us to explore the role that EBV and/or HHV-6 may play in CFS.

HERV-K18 env as a risk factor for CFIDS

Investigator: Brigitte T. Huber, PhD, Tufts University School of Medicine, Boston, MA
Budget: $60,000

It is believed that chronic fatigue and immune dysfunction syndrome (CFIDS) may be caused by multiple genetic and environmental factors, resulting in an abnormal immune response. The herpesvirus Epstein Barr Virus (EBV) has been suggested to be associated with CFIDS, although this concept is far from accepted. Dr. Huber believes that EBV transactivates an endogenous superantigen, HERV-K18. Superantigens constitute a class of proteins capable of deregulating the immune system. EBV is an outstanding model for studies because it is an ubiquitous herpesvirus that has successfully adapted to the human population at large with lifelong viral persistence. Although benign in healthy individuals, EBV is an oncogenic virus that leads to various malignancies in immunosuppressed or genetically predisposed hosts.

In their 2004-2005 Association-funded pilot study, Dr. Huber and her research group discovered a strong correlation between infectious agents, CFIDS, and the presence of a particular HERV-K18 allele, opening a new dimension in the collective understanding of the diverse interactions that take place between an infectious virus and the immune system of its host. With the new funding in 2006, Dr. Huber will significantly expand the size of the patient sample groups to unequivocally determine whether a correlation exists between the presence of the specific HERV-K18 allele, a particular infectious disease and the development of CFIDS. Collaborators on the 2006 study include Dr. Andrew Lloyd, University of New South Wales, Australia and Dr. Renee Taylor, University of IL at Chicago.

In 2007, Dr. Huber and collaborators were awarded a five-year grant from the National Institutes of Health to expand investigations of the role of HERV-K18. Read more about her grant at http://www.cfids.org/cfidslink/2007/100303.asp?tr=y&auid=3058017.

Mechanisms of Cytotoxic Cell Dysfunction in CFS

Investigator: Nancy Klimas, MD, University of Miami, Miami, FL
Budget: $60,000

Dr. Klimas and her multidisciplinary research group will look at possible mechanisms of immune system dysfunction and correlate those findings with symptom cluster and severity. They will focus on a membrane associated peptidase, dipeptidyl peptidase IV, also known as CD26 and a key neuropeptide, neuropeptide Y, as they relate to cytotoxic function in patients with CFS. A function of this peptidase is to regulate levels of neuropeptide Y. Neuropeptide Y is remarkable in the context of CFS, as it has been demonstrated not only to cause defects in NK and T cell function when it is elevated, but also has roles in the inflammatory process, cardiorespiratory system, nervous system and endocrine system. Neuropeptide Y is stored in the same cells that release adrenaline during an autonomic response, which is known to be abnormal in CFS. In animal models, neuropeptide Y can induce a lower body temperature, fatigue and reduced activity levels. In studies of patients with major depression, neuropeptide Y is shown to be elevated. There are also studies that link the response of an over active sympathetic nervous system to low natural killer cell function and elevations of neuropeptide Y. Preliminary data indicates that in CFS patients CD26 is depleted, most likely through chronic cellular activation. Therefore, low CD26 will produce elevated levels of the peptide, resulting in immune dysfunction and ultimately, the symptoms of CFS.

1H MRS Neurometabolites as Diagnostic Markers for Chronic Fatigue Syndrome: Comparison with Major Depressive Disorder and Healthy Volunteers

Investigator: Dikoma C. Shungu, PhD, Weill Medical College of Cornell University, New York, NY
Budget: $59,950

Dr. Shungu and his research group continue to assess measurements of certain brain chemicals or neurometabolites with a technique known as proton magnetic resonance spectroscopy (1H MRS). Dr. Shungu believes the 1H MRS could serve as a screening test or diagnostic marker for chronic fatigue syndrome (CFS).

Currently, the diagnosis of CFS is made only after alternative medical and psychiatric causes of the symptoms have been excluded. A major factor complicating a CFS diagnosis is that symptoms often overlap with common mental or psychiatric disorders.  With financial assistance from the Association in 2004-2005, they conducted studies which aimed to determine whether there were measurable differences in the levels of specific brain chemicals between CFS and generalized anxiety disorder (GAD). Their theory was that if such brain chemical differences exist between CFS and overlapping psychiatric conditions then health care providers could use these differences as the basis for developing 1H MRS as a non-invasive clinical tool for screening or diagnosing CFS. Analysis of the data from the completed study comparing CFS and GAD patients yielded potentially diagnostic differences between the two disorders: (a) lactic acid is significantly elevated in the cerebrospinal or brain fluid of CFS patients compared to people with GAD or healthy volunteers; this strongly suggests that there might be a brain energy production and utilization problem in CFS; and (b) levels of brain lactic acid were highly correlated with fatigue severity across all subjects, and that they were specifically tied to fatigue severity but not to anxiety or depression symptoms.

With continued funding, Dr. Shungu plans to repeat the exact methods successfully implemented in the CFS-GAD research to compare levels of brain chemical in those with CFS and major depressive disorder (MDD) patients and in age- and sex-matched healthy controls. There are several features of MDD that make it an important comparison group with CFS, but two of these in particular stand out: (1) MDD is more prevalent among CFS patients than GAD, and (2) the symptoms of CFS more highly resemble those of MDD than GAD. They hope that after completing the comparisons between CFS and the two overlapping and confounding psychiatric disorders, the differences found in the brain chemicals can be helpful in improving the ease of diagnosing CFS.

Using an Exercise Challenge to Investigate the Pathophysiology of CFIDS

Investigators: J. Mark VanNess, PhD, and Christopher Snell, PhD,University of the Pacific, Stockton, CA
Budget: $60,000

The extreme fatigue following physical exertion often prompts physical activity avoidance behaviors in CFIDS patients. However, when physical activity is unavoidable, given sufficient advance notice, CFIDS patients have learned to prepare by resting ahead of time. This enables them to cope well with the activity, but usually results in subsequent relapse. The use of such coping strategies prior to undergoing clinical exercise testing may be responsible for the mixed results sometimes obtained in research studies. In previous trials, Dr. VanNess and Dr. Snell observed that many CFIDS patients can perform a maximal exercise test with results similar to sedentary but otherwise healthy individuals. The differences are seen when patients perform a second exercise test within the same 24-hour period. Physical function is significantly reduced in CFIDS patients whereas healthy individuals are able to repeat the test with similar results. In the current study Dr. VanNess and Dr. Snell will use a double-test strategy to study post-activity symptoms in CFIDS. Various measures of biological, physical and mental function will be taken prior to and following the initial test and again after the second test. These results will be compared between patients and healthy individuals in an attempt to better characterize post-exertion effects in CFIDS and provide insights to the origins of these effects.