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Chronic Fatigue Research at Chronic Fatigue Research at the NIHthe NIH
Prepared for the DHHS Secretary’s Advisory Committee on CFS
July 17, 2006
IntroductionIntroduction
NIH has sponsored CFS research for many years and remains committed to increasing the amount and quality of research
NIH supports investigator initiated research in response to various types of program announcements
It is only through an increase in meritorious proposals that funding can and will increase
Program HistoryProgram History
Through September 1999, NIAID had sole responsibility for this program
October 1999, Drs. Varmus and Fauci recognized the need for a multidisciplinary and integrated approach encompassing the missions of many ICs
Program was incorporated into the Office of the Director
History, continuedHistory, continued
Dr. Donna Dean was appointed to coordinate these efforts for the NIH. A complicating factor was that she also served as co-chair of the DHHS CFS Coordinating Committee
Under her direction, the ORWH sponsored a State of the Science Symposium for this committee which held its last meeting in 2001 at which time she transitioned out of her position, and I assumed the coordinating role for NIH.
Accomplishments since April Accomplishments since April 20012001
NIH pursues integrated, multidisciplinary, and interdisciplinary research efforts through a Trans-NIH Working Group for Research on Chronic Fatigue Syndrome chaired by me for Dr. Vivian Pinn, the Associate Director of NIH for Women’s Health
Working Group developed an action plan to enhance the status of CFS research at the NIH and among the external scientific community
Accomplishments, continuedAccomplishments, continued
Program Announcement based on recommendations from State of the Science Symposium
Scientific Workshop: Neuroimmune mechanisms and Chronic Fatigue Syndrome: Will understanding central mechanisms enhance the search for the causes, consequences and treatment of CFS?
Establishment of Special Interest Group on Scientific Integrative Medical Research to promote intramural interest.
Impetus for WorkshopImpetus for WorkshopTopic SelectionTopic Selection
Need to explain the diverse and conflicting research literature on CFS that agrees only in that there is neither a known identifiable cause nor a cure for CFS
Intrigued by the positive effects of behavior and exercise therapies, as well as medications that act on the brain and central nervous system, in the management of many medical conditions including CFS
Exciting new possibilities now exist for exploring the relationship of brain science and immune dysfunction
Accomplishments, continued Accomplishments, continued
Publication of Science Series, first issue of which is Chronic Fatigue Syndrome: Efforts by the NIH to understand CFS and plan for future research.
First integrated NIH CFS website explaining our mission, efforts, and containing information for both the public and scientists. Also includes a link to a pub med search on CFS that can be customized by the user.
http://orwh.od.nih.gov/cfs.html
Accomplishments, continuedAccomplishments, continued
Neuroimmune Mechanisms and Chronic Fatigue Syndrome: Will understanding central mechanisms enhance the search for the causes, consequences, and treatment of CFS? (NIH Publication No. 04-5497)
RFA OD-06-002 to explicate how the brain as the mediator of the many systems involved in , fits into the schema for understanding CFS.
Specifically solicited proposals from multidisciplinary Specifically solicited proposals from multidisciplinary teams of scientists to develop an interdisciplinary teams of scientists to develop an interdisciplinary approach to this topic.approach to this topic.
Accomplishments continuedAccomplishments continued
29 Applications were received and reviewed7 have been encumbered Calls for an annual meeting of awardees to
further integration of findings and encourage further collaboration
WG will convene to begin planning investigators’ meeting for 2007 and use this as a base for furthering collaborations
Encumbered applicationsEncumbered applications
Proteomics of cerebrospinal fluid in CFSFunded by NIEHS Promises to provide the first predictive
model of CFS based on objective proteomic measures and may ultimately point towards a unified pathogenesis for CFS.
Highlights of research Highlights of research contributionscontributions
Epidemiologic studies that demonstrated demonstrated the need to broaden the population base for the study of CFS to reflect diversity in age, sex, and racial/ethnic background
First large scale population analysis of data from the Swedish Twin Registry to elucidate basic questions about CFS and quantify genetic and environmental sources of variation
Highlights continuedHighlights continued
One of the first analyses of CFS patients using state of the art proteomic technologies identified specific protein markers in spinal fluid suggesting a common central nervous pathophysiology found in CFS and PGWI
Pathophysiology and pathogenesis of orthostatic intolerance and its role in producing symptoms of CFS
Study of MZ twins discordant for CFS has the potential to identify biomarkers and identify testable hypotheses
Highlights continuedHighlights continued
Studies of blood flow, blood volume, and red blood cell mass to determine their roles in CFS and to develop treatments
Seminal and promising work in understanding role of cytokines
Role of low levels of enteroviral double strand RNA in pathogenesis of CFS
Highlights continuedHighlights continued
Clinical trials to develop and test cognitive behavioral and exercise treatments
Study of hindbrain malformation that impairs cerebral spinal fluid flow and syringomelia, a cavitation in the spinal cord, in an attempt to explain and treat disabling fatigue in CFS and FM patients
Highlights continuedHighlights continued
Intramural patient-oriented research in clinical neurocardiology that focusses on the etiology, pathophysiology, diagnosis and treatment of autonomic nervous system disorders commonly found among CFS patients
Prospective interdisciplinary study exploring the development of CFS in adolescents with mononucleosis
Basic studies of effects of chronic stress and disease Basic studies of CNS serotonin system
Looking AheadLooking Ahead
Major effort to revitalize intramural interest group Plan for Investigators’ meeting as base to build
future alliances and interdisciplinary efforts Program Announcement will be updated and
reissued Continue to work collaboratively within and
outside NIIH, especially to encourage new researchers and interest in other NIH initiatives
Applications to be reviewed in Applications to be reviewed in AugustAugust
1H/31P MSRI assessment of mitochondrial dysfunction in CFS
Behavioral insomnia treatment in CFS Central augmentation of pain processing in chronic
low back pain ERK activation in female orofacial pain syndromes Exercise and sleep restriction: predicting
susceptibility to CFS/FM symptoms Stress, virus infection and CFS
Exercise-based motivational interviewing for fibromyalgia Family, employment demands and health in fibromyalgia Immunologic mechanisms, biomarkers and subsets in CFS Peripheral and central mechanisms of pain in fibromyalgia Primary afferent receptors mediating fatigue and myalgia Role of ASICS in the etiology of fibromyalgia Translating fibromyalgia HR-QoL research into practice
IMPORTANT WEBSITESIMPORTANT WEBSITES
http://orwh.od.nih.gov/cfs.htmlhttp://orwh.od.nih.gov BIRCWH & SCORhttp://grants1.nih.gov/grants/oer.htmhttp://opasi.nih.gov
Encumbered Applications, Encumbered Applications, continuedcontinued
Neuropeptide Y and dipeptidylpeptidase IV (CD 26) in CFS
Cognitive behavioral stress management for cfs Mast cells, antidepressants and cfs Autonomic nervous system in cfs Stress and neuroimmune dysregulation in cfs Human spinal cord glial cytokines and fm pain