Mitochondrial Dysfunction and Gulf War Illness
Abstract
Rationale: The cause of Gulf War illness (GWI) is unclear, and the symptoms are complex. This makes diagnosis and treatment difficult. However, many of the symptoms are similar to those observed in patients with mitochondrial diseases caused by genetic deficiencies. Problems with mitochondria, which produce most of our energy, can lead to exercise intolerance, fatigue, and neurological symptoms -- symptoms that are also common in GWI. In addition, mitochondria are affected by many of the toxic chemicals to which a large number of Veterans were exposed. Therefore, we wish to investigate whether mitochondria function poorly or show damage in patients with GWI. Objective: The objectives of our proposed experiments are to test whether mitochondria from circulating blood cells are damaged or function poorly in Gulf War Veterans. Preliminary tests suggest that this is the case. If so, this would both suggest that an underlying cause of GWI is damage to mitochondria and that testing of mitochondria in blood cells from Veterans could aid in the diagnosis of GWI. We also plan to investigate whether mitochondrial tests are consistent over time and how much they are affected by exercise, diet, and history of exposure to chemicals such as pesticides during the Gulf War. Applicability: Our goal is to produce research that reduces suffering associated with GWI. If we find that mitochondria are in fact damaged in blood cells of veterans with GWI, this will: (1) Help patients including: (a) Veterans who currently suffer from GWI by improving diagnosis (analysis of mitochondria in blood will make detection of GWI more accurate); (b) Veterans who currently suffer from GWI by improving doctors ability to monitor symptom improvement with medicinal or other therapies; (c) Veterans who currently suffer from GWI by testing whether therapies being developed for genetically based mitochondrial diseases might also help Veterans with GWI; (d) future Veterans by testing whether Veterans who were more highly exposed to chemicals that contribute to GWI (pesticides, pyridostigmine bromide, and air pollution) have greater mitochondrial deficits. If so, this will be informative in terms of reducing such exposures GWI or GWI-like illnesses in the future. (2) Provide clinical benefits including a relatively rapid and objective blood-based test of mitochondrial health that might be useful to diagnose severity of GWI, as well as to test improvement following therapy. (3) Provide motivation for testing mitochondrial therapies in future work with a time horizon of 3-5 years. We propose a 3-year study. If our results are positive, upon completion of the study, we will propose future tests of the therapeutic potential of drugs designed for mitochondrial disease, as well as non-drug-based therapies such as dietary changes and exercise therapy. (4) Contribute to the basic understanding of GWI and advance GWI research. This work will permit a statistically powerful test of whether mitochondrial damage is a characteristic of GWI. GWI is a complicated disease, and we do not suggest that it can be entirely explained by mitochondrial damage. However, we do believe that mitochondria could be very important, and mitochondria are currently studied only very minimally in the context of GWI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610663
Entities
People
- Joel N. Meyer
Organizations
- Duke University
- United States Army