Validation of a Novel Glycan Conjugate as a Safe Treatment Option for Gulf War Illness Veterans by Expanded Evaluation Efforts
Abstract
Gulf War Illness (GWI) is a devastating condition suffered by a third of the nearly 700,000 American Soldiers who served in the 1990-1991 war. These Veterans have multiple symptoms that include memory and cognitive deficits, 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, gastrointestinal dysfunction, among others, become even more pronounced. Thus, there is an urgent need to test and develop safe and effective therapeutic agents that will help alleviate the maladies 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 both health and disease. If this normal communication goes arwy, 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 support that the immune system normally provides to the brain. Such immune system-mediated brain damage might be responsible for many functional neurological problems, such as learning and memory deficits. Multiple studies with GWI Veterans report immune system irregularities, which are consistent with the pattern of immune system changes associated with other major neurological diseases. There are also recent studies in models of GWI, including one from our group, that suggest that the gut microflora composition is dysfunctional and it might be the reason for not only gastrointestinal but also some of the neurological deficits. 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, while also restoring the normal gut microflora balance, is desired. Finally, while there are female Veterans with GWI, the scientific community has not devoted the needed attention to studying GWI or testing possible therapies in females. Our goal in the project described in this application is to address all these gaps. To achieve our goal, we will use our expertise and preliminary findings in two different models of GWI that we obtained with a novel treatment option we have at our disposal. This is a modified sugar-based molecule, which is found in human milk and is secreted during lactation in large quantities. This sugar-based molecule and other similar molecules were recently given a GRAS (Generally Recognized as Safe) status by regulatory agencies in Europe and the United States. Our preliminary findings in GWI models also indicate that it is safe after long-term treatment. Importantly, in these GWI models we have shown that many problems with brain function caused by GWI exposures are not seen if we treat the animals with this molecule. We also have preliminary findings, some just published, indicating that gastrointestinal microflora becomes inflammatory in nature months after GWI exposures have ended. Importantly, our therapeutic molecule reverses these deleterious changes and restores the healthy state of the microflora. Based on our hands-on experience and relevant preliminary data, with this application we propose to expand our testing and validation of this molecule in GWI models by evaluating its potential to restore the normal gut microflora in both females and males. To bring this potential therapeutic closer to testing in GWI Veterans, we will evaluate the effectiveness of the treatment if we give it by application into the nose; such application would be easier to implement in patients with GWI. We will also test if we stop the treatment with this molecule after a period of time to whether its benefits will continue to exist; this
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110661
Entities
People
- Nikolay Filipov
Organizations
- The University of Georgia
- United States Army