GWI: Molecular Analysis of Disease Endophenotypes and Response to Acupuncture Treatment
Abstract
Gulf War Illness (GWI) remains a poorly understood disease state characterized by a constellation of symptoms that may last for decades and affect multiple organs. The prevailing notion, based primarily on epidemiologic research but further supported by studies in animal models, is that toxic environmental exposures during deployment may have triggered in susceptible individuals various autonomic, neuroendocrine, and immune dysfunctions responsible for their symptomatology and their overall poor quality of life. It is also well accepted that lack of a deeper knowledge of the underlying disease causes has hampered the development of more effective treatments for GWI. Furthermore, it is quite plausible that because of lack of any kind of a diagnostic test for GWI, some patients are devoted of the right treatment for their symptoms due to misdiagnosis. Indeed, in the current application, we have brought together scientists with complementary expertise in diverse diseases, the symptoms of which often overlap with those of GWI, and with access to cutting-edge technology that will allow, for the first time to our knowledge, a large-scale unbiased screening of the blood of patients with GWI. The goal of this analysis is to identify a protein (or proteins) that is unique to GWI compared to other diseases and can provide the basis for a GWI diagnostic blood test. Depending on the nature of the identified proteins and what is known about their biology, it is anticipated that their discovery will also shed light to the elusive causes of GWI and pave the way for the development of highly efficacious therapies for this illness. The second goal of this application takes advantage of an excising infrastructure in an effort to make the best use of federal resources as well as medical information and blood samples offered by GWI for research purposes during a previously conducted study by one of the investigators of our group. That study was investigating the therapeutic potential of acupuncture treatment in 104 Veterans with GWI and clearly demonstrated beneficial effects of a 6-month course of acupuncture, most notably significant reductions in pain scores. Pain, in particular, has a disproportionate negative impact in the overall quality of life in Veterans, resulting in many of them to turn to self-medication through drug and alcohol abuse in order to find alleviation from their symptoms. It is thus particularly encouraging the finding, from the same study, that GWI patients demonstrated extremely favorable attitudes toward acupuncture from a consumer point of view, indicating that the introduction of acupuncture into the Department of Veterans Affairs system would be heavily utilized in the near future. However, the reality is that only a fraction of patients treated with acupuncture will actually improve. Being able to predict using a simple blood test which patients are more likely to become symptom-free in response to acupuncture is another goal of this proposal. We will screen blood samples for this purpose, as described above for the development of the diagnostic test, but for this analysis the patients will be grouped to acupuncture responders and non-responders and the unique biologic signatures of each group will be identified. In parallel, two different samples from the same patient, one prior and the second upon the completion of the course of acupuncture, will be compared in order to gain important knowledge on how acupuncture works. Uncovering underlying mechanisms of acupuncture effects is the first step towards devising ways to potentiate them, satisfying thus an unmet need in the GWI therapeutics and beyond. Among the unique qualifications of our research team is that we are well equipped to validate findings emerging from this line of investigation using additional well-characterized patient cohorts but most importantly to further refine them using animal models. This bedside-to-bench research philosop
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610528
Entities
People
- Efi Kokkotou
Organizations
- Beth Israel Deaconess Medical Center
- United States Army