DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Understanding Gulf War Illness: An Integrative Modeling Approach

Principal Investigator: MORRIS, MARIANA
Institution Receiving Award: NOVA SOUTHEASTERN UNIVERSITY
Program: GWIRP
Proposal Number: GW120045
Award Number: W81XWH-13-2-0085
Funding Mechanism: Consortium Award
Partnering Awards:
Award Amount: $4,102,527.00


PUBLIC ABSTRACT

The goal of the GWI consortium is to develop a better understanding of GWI and identify specific disease targets to find treatments that will address the cause of the disease and not just treat the symptoms associated with the disease. Current treatments used for GWI only treat the symptoms associated with the disease and do not target the underlying disease process. This consortium will integrate our clinical understanding of the disease process with basic research efforts using a novel mathematical model. The use of this mathematical model or computational biology approach will enable the consortium to quickly identify targets of dysfunction and find treatments that will address the causes of the disease.

It has been established that GWI is caused by a disruption in normal cell signaling that results in disabling symptoms including fainting, low blood pressure, fatigue, and pain. This is primarily due to disruptions in normal immune, cardiovascular, and hormone signaling. However, the exact cause of this disruption is not well understood. It is the goal of the consortium to pinpoint the causes of the disease and tailor treatment more effectively. Specifically, our more detailed understanding of the dysfunction involved in GWI would greatly speed up the identification of promising targets to help improve diagnosis and treatment of GWI.

In an effort to quickly identify disease targets and find effective GWI treatments, this consortium uses a computational biology approach that combines data derived from animal models of GWI and humans. It is possible that some of the drugs selected on the basis of the animal studies and mathematical modeling may not be applicable to humans. However, our model is capable of testing a series of targets and drugs and is only limited by time. Our approach takes into account several alternatives, with different targets.

The exciting part of this consortium is that the computational biology approach that ties the clinical and basic research understanding of the disease together will enable very quick identification of disease targets and effective treatments. This approach will rapidly screen potential candidate treatments that impact the disease process. By using this approach, the consortium will create a short list of attractive known and Food and Drug Administration-approved drugs that could be tested rapidly in clinical trials without requiring a drug development effort. However, we will also be able to identify highly effective disease targets that could also lead to drug development. At the end of the 4-year study, the consortium will have completed early studies in human patients that will provide insight into disease targets and effective treatments, enabling the design of larger-scale clinical trials for further drug testing.

By increasing the understanding of the reasons for GWI, our consortium will advance the diagnosis and treatment of the disease. Specifically, our more detailed understanding of the dysfunction involved in GWI would greatly increase the speed to identify targets for improved diagnosis as well as selection and testing of more specific treatments over the longer term that will address the causes of disease.