Abstract
BackgroundGulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline.MethodsHere, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module’s constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses.ResultsWe found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these.ConclusionOf the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0111-3) contains supplementary material, which is available to authorized users.
Highlights
Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found
In this work we found 19 of the 4,620 gene expression modules (~0.4 %) to be differentially expressed in GWI compared to healthy controls
Collectively this work supports a treatment strategy that would target both immune and sex hormone signaling in GWI
Summary
Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline. The repurposing of Food and Drug Administration (FDA) approved drugs offers a fast cost effective solution for discovering. Gulf War Illness (GWI) is but one example of a complex chronic illness with no known cure and which requires long-term treatment and monitoring. This both prolongs patient suffering and increases the financial burden of the illness, for the individual, the family and society. Since returning from the first Gulf War over 20 years ago investments of nearly $1 billion have been made to Gulf War Veterans health [6], there is still no effective treatment available for the nearly 250,000
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