Evaluation of Treatment Efficacy with a Potent Novel Immunomodulatory Glycan Conjugate in Gulf War Illness Models
Abstract
Gulf War illness (GWI) is a condition suffered by at least 25% of the nearly 700,000 American Soldiers who served in the 1990-1991 war. These Veterans have multiple symptoms that include memory and cognitive problems, as well as immune system-related problems. Exposure of the Soldiers to pesticides, anti-nerve gas pills, and low-level of nerve gas, plus the stress of war itself, are believed to responsible for the illness. Decades after exposures have ended, there is no diminution of the symptoms. In fact, as the Veterans age, learning and memory problems, among others, become even more pronounced. Thus, there is an urgent need to test and develop safe and effective therapeutic agents that will help alleviating the neurological deficits the GWI Veterans suffer from every day of their lives. There is strong scientific evidence that the brain and the immune system communicate with each other and do so in health and disease. If this normal communication goes array, problems arise. For example, if the immune system is inappropriately activated, it could damage the brain by increasing the level of brain inflammation and decreasing the level of normal support that the immune system normally provides to the brain. Such immune system-mediated brain damage might be responsible for many functional problems with the brain, such as learning and memory deficits. There are multiple studies with GWI Veterans that report immune system irregularities consistent with the pattern of immune system changes associated with other neurological diseases. This is why coming up with a safe treatment strategy that is directed towards restoring the immune system balance and eliminating the immune system-mediated detrimental effects on the brain is an important and supported by the existing science goal; this is our goal in the project described in this application. To achieve our goal, we will use our expertise and preliminary findings that we have with a novel treatment option that we have at our disposal. This treatment option has been tested in animal models of other neurological diseases, such as multiple sclerosis, and its beneficial effects were remarkable. In addition, we have preliminary results in laboratory animals indicating that this treatment has a positive influence on learning and memory. Based on our hands-on experience and relevant preliminary data, with this application we propose to test a novel, likely extremely safe therapeutic agent, that is made entirely of sugars. Importantly, this sugar-based molecule is a component of human milk and is secreted during lactation in large quantities. This therapeutic agent, when given to experimental animals, produces no measurable side effects and it restores the immune system balance. Because this agent has not been tested in a GWI exposure-relevant scenario, we will first test its therapeutic ability in two different mouse models of GWI. One of the models uses only pesticide and anti-nerve gas pills combination; the other model uses anti-nerve gas pills, insect repellent, nerve gas analogue, and stress to simulate GW exposures. It is important to use two different models of GWI as not all Soldiers were exposed to nerve gas; this way, we will be able to test this treatment strategy in animal models applicable to different subsegments of the Veterans with GWI. Because GWI chemical exposures were decades ago and the Veterans with GWI need help now, we will have animal treatment groups where the therapy with this sugar starts months after chemical exposures have ended. We will use behavioral and many other tests to determine the benefits of this treatment for improving brain function and restoring the normal balance of the immune system. This study will test novel sugar-based therapy, a sugar normally found in human milk, with demonstrated therapeutic properties for several highly relevant to GWI immunological and neurological deficits. Due to its ability to restore nor
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610586
Entities
People
- Nikolay Filipov
Organizations
- United States Army
- University of Georgia