Research studies conducted over the last decade provide compelling evidence that Gulf War Illness (GWI) may have been caused by exposure to chemicals, such as an anti-nerve agent pyridostigmine bromide (PB) and different types of pesticides (GW agents). These studies also show that brain structures that are involved in processing and storing memory, as well as brain pathways involved in controlling pain and fatigue, are altered in GW Veterans with this condition. Even now, nearly 25 years later, Veterans with GWI continue to experience these complex symptoms, and this illness remains difficult to diagnose since the current GWI diagnostic process are limited by having to use information on self-reporting of symptoms. As such, there remains a need for developing minimally invasive blood-based disease markers (biomarker) of GWI. The goal of this current study is to identify novel biomarkers of GWI that can assist physicians in providing an objective diagnosis of GWI so that appropriate clinical evaluations and treatments can be provided to GW Veterans with this condition. Another key goal of this project is to identify biomarkers of GW chemical exposure and symptom profiles so that care and treatment can be tailored individually for each Veteran with GWI.

Scientists working in the field of GWI research continue to provide strong evidence that this condition is connected with irregular responses by blood cells that generally combat irritations or other injuries to the body (inflammation). Scientists have also found that GWI could also be due to damage to mitochondria, known as the powerhouses responsible for generating energy through the breakdown of sugars and fats (lipids). Scientists at the Roskamp Institute have developed mouse models of GWI in order to identify biomarkers of brain damage and neurobehavioral problems that are a direct consequence of chemicals to which GW Veterans were exposed during the 1991 GW. They have identified that there might be problems with breaking down fats in the brains of exposed mice even long after subacute exposure to GW agents. In particular, they show changes in lipids that belong to cellular compartments (peroxisomes) that perform tasks similar to those of the mitochondria with respect to the breakdown of fats.

The inflammatory processes, mitochondria, and peroxisomes display unique lipid classes that can be measured in blood using mass spectrometry technologies. These technologies allow us to detect and measure elemental composition of each lipid. We plan to use this technology to study lipids that are specific to inflammation and metabolic disturbances associated with GWI in order to determine if they can be used as biomarkers of GWI. In collaboration with the Boston GWI consortium, we are testing this hypothesis, and our early pilot work in control and GWI Veterans support potential use of these lipids as biomarkers of GWI. The proposal will expand these pilot studies and determine if lipids associated with these key disturbances in GWI can be useful tools for diagnosing GWI. The proposal will also try to use these lipids in order to identify subgroups of GW Veterans with similar chemical exposures and symptom patterns. This work will also be facilitated by the use of blood samples from GWI animal models that will help with translational studies linking animal model work and human studies. This will help fill the gaps between the two so that future studies can be conducted that can use these biomarkers to determine if treatments and care designed for GWI are succeeding. Furthermore, identifying biomarkers of exposures and symptom profiles will help with delivering personalized care and treatment to each Veteran appropriately.

The existing expertise and collaborations between the Roskamp Institute and the Boston GWI consortium will expedite successful translation of this endeavor so that appropriate biomarker tools are made available to the clinicians in order to assist them with diagnosing GWI and ensuring that appropriate medical plans are developed for the care and treatment of Veterans with GWI.