Posted November 13, 2018
Dr. Nancy Klimas, M.D., Nova Southeastern University and
Dr. Kimberly Sullivan, Ph.D., Boston University
Nova Southeastern University
Gulf War Illness (GWI) is a chronic, multi-symptom illness that affects Veterans of the 1990-1991 Gulf War. Because the symptoms of GWI vary from person to person, it has been difficult to determine the number of Veterans with GWI; however, multiple studies have estimated the prevalence to be 25%-32%.1 Recent research suggests that dysfunction in the central and autonomic nervous system, cellular energy production, and oxidative balance, as well as changes to the neuroendocrine and immune systems all contribute to GWI; however, further studies are required to determine the underlying pathobiological mechanisms of GWI.2
In 2012, the Gulf War Illness Research Program (GWIRP) granted two Consortium Awards, one to a team of investigators led by Drs. Mariana Morris, Nancy Klimas, and Gordon Broderick at Nova Southeastern University and another led by Dr. Kimberly Sullivan at Boston University. These GWI consortia brought together a diverse group of experts with the goal of executing preclinical and clinical studies that would increase understanding of the mechanisms responsible for mediating GWI and lead to the discovery of potential therapeutics for Veterans with GWI. The Nova Southeastern consortium focused on identifying candidate treatments by merging preclinical animal model studies comparing cytokine, hormone and neuropeptide expression profiles with advanced computer simulations of aberrant metabolic activity. Based on these findings, Dr. Klimas and her team selected a combination treatment strategy that targets the inflammation and endocrine dysfunction observed in GWI now being evaluated in a Phase I study of Veterans with GWI. The treatment consists of entanercept, a tumor necrosis factor receptor antagonist, and mifepristone, an anti-glucocorticoid. Major findings of the Boston University consortium include strong evidence for a neuroinflammatory component in GWI in animal models as well as significant differences between the immune cells of Veterans with GWI and controls. The results gathered by these consortia have provided a critical step forward in understanding the pathobiological mechanisms responsible for GWI and have produced key evidence to support the use of specific therapeutics to treat Veterans with GWI.
In September 2018, Dr. Klimas received a GWIRP Clinical Consortium Award. The objective of the Gulf War Illness Clinical Trials and Interventions Consortium (GWICTIC) is to combine the expertise and efforts of the two previous consortia and build upon their results by implementing early-phase clinical trials to evaluate candidate therapeutics for GWI. The GWICTIC aims to execute five Phase I or Phase II clinical trials in the four year period of performance. The first set of trials will extend the initial evaluation of the entanercept plus mifepristone treatment carried out by the original consortium. Subsequent interventions will target additional pathobiological mechanisms elucidated by the prior consortia efforts.
In addition to her participation as a co-investigator on Dr. Klimas’ Clinical Consortium Award, Dr. Sullivan will use her 2017 Biorepository Resource Network Award to work toward creating the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN), which will house previously and newly collected biological specimens and clinical data from Veterans with GWI and control subjects. BBRAIN will harness the biorepository infrastructure created by Dr. Sullivan’s previous consortium to create a resource for all GWI researchers.
Novel treatment strategies and objective markers of GWI are critical needs for the GWI community. The GWICTIC will help meet these needs by establishing a streamlined infrastructure for conducting Phase I and II clinical trials to evaluate potential GWI therapeutics, while the new BBRAIN will provide a key resource for the exploration of mechanisms, identification of biomarkers, and selection of innovative treatment strategies for GWI. With these new projects, Drs. Klimas and Sullivan will continue fostering and creating a collaborative environment for researchers interested in unraveling the mysteries of GWI.
List of GWICTIC trial sites:
Palo Alto VA War Related Illness and Injury Study Center (WRIISC)
Nova Southeastern University – Institute for Neuro-immune Medicine
New Jersey VA WRIISC
James J. Peters VA Medical Center
Rochester General Hospital
1 White RF, Steele L, O’Callaghan JP, et al. 2016. Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment. Cortex 74:449-475.
2 Research Advisory Committee on Gulf War Veterans’ Illnesses. 2014. Gulf War illness and the health of Gulf War veterans: Research update and recommendations, 2009-2013. Washington, DC: US Government Printing Office.
Abstracts for Dr. Klimas
Public and Technical Abstracts: The Gulf War Illness Clinical Trials and Interventions Consortium (GWICTIC)
Public and Technical Abstracts: Understanding Gulf War Illness: An Integrative Modeling Approach
Abstracts for Dr. SullivanPublic and Technical Abstracts: Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI
Public and Technical Abstracts: Brain Immune Interactions as the Basis of Gulf War Illness: Gulf War Illness Consortium (GWIC)