The early news comes as the result of an ongoing study funded by the treatment-focused Gulf War Illness Research Program (GWIRP), part of the Congressionally Directed Medical Research Program (CDMRP) within the U.S. Department of Defense.
The study, funded in 2014 with FY13 funds, is entitled: "Monosodium Luminol for Improving Brain Function in Gulf War Illness monosodium luminal for cognitive dysfunction and neuroinflammatory-caused depression." (GW130037) The principal investigator, Dr. Ashok Shetty, is at the Texas A&M University System Health Science Center.
According to the proposal's abstracts:
Gulf War Illness (GWI), observed in nearly 30% of the 700,000 Persian Gulf War-1 (PGW-1) veterans, is characterized by multiple chronic health problems, which also include brain-related impairments. The most conspicuous brain impairments include learning difficulties, inability to make new memories, depression, anxiety, and lack of concentration. Multiple possible causes have been suggested for this disease over the last two decades. A detailed report by the VA Research Advisory Committee (VA-RAC) on GWI suggests that the symptoms exhibited by a major fraction of PGW-1 veterans are most likely owed to an exposure to chemicals such as pyridostigmine bromide (PB) and pesticides such as DEET and permethrin (PM) during the war. These exposures were believed to have occurred due to the following circumstances: First, to reduce the devastating effects of a possible nerve gas attack during the war, the troops were given pyridostigmine bromide (PB) as a prophylactic treatment. Second, pesticides such as DEET and PM were widely used by troops on skin and uniforms to combat insects and rodents in the region. Causes of GWI in some veterans likely also include exposure to chemical weapons (especially for those veterans who were stationed near the chemical weapon depot demolitions). Thus, it is widely believed that the neurological symptoms in a vast majority of Gulf War veterans are owed to a synergistic interaction of chemicals PB, DEET, and PM, or interaction of one or more of these chemicals with war-related stress. Indeed, studies performed in our laboratory using a rat model showed that combined exposure to low doses of chemicals PB, DEET, and PM, with or without mild stress, for 4 weeks, causes considerable dysfunction of the hippocampus, a region of the brain important for maintenance of normal memory and mood function. These include learning difficulties, reduced ability for making and retrieving new memories, increased depressive and anxiety-like behavior. Importantly, these changes were associated with chronic inflammation and greatly reduced neurogenesis (daily generation of new neurons) in the hippocampus. Because daily addition of new neurons to the hippocampus circuitry is an important process that contributes towards formation of new memories and maintenance of normal mood function, it is likely that greatly reduced hippocampal neurogenesis at least partly underlies the memory and mood impairments observed in this GWI model.
Furthermore, other studies have shown that exposure to GWI-related chemicals can cause increased oxidative stress (i.e., increased concentration of free radicals capable of causing adverse effects on neuron/brain function). Because both inflammation and oxidative stress can adversely affect cognitive and mood function either directly or indirectly through suppression of new neuron production (neurogenesis) in the hippocampus, it is likely that chronic inflammation and oxidative stress are among the major causes underlying cognitive dysfunction, depression, and anxiety in GWI. From this perspective, strategies that are capable of suppressing inflammation and oxidative stress have promise for enhancing both hippocampal neurogenesis as well as cognitive and mood function in GWI. Therefore, in this project, using an animal model of Gulf War illness, we will rigorously test the efficacy of a drug called monosodium luminol-GVT (MSL-GVT, obtained from Bach Pharma) for easing cognitive dysfunction, depression, and anxiety in a rat model of GWI. Thus, the major focus of this project is on developing a therapy that is likely to be useful for both improving the learning and memory function and reducing depression and anxiety in PGW-1 veterans exhibiting GWI.
Impact: This project proposes to evaluate the efficacy of a drug (MSL-GVT) having potent anti-inflammatory and anti-oxidant properties for improving cognitive and mood function and hippocampal neurogenesis in a rat model of GWI. The chosen prototype of GWI has been well characterized and simulates exposures encountered by significant fractions of veterans during the PGW-1. Thus, studies proposed in this project are highly relevant for the treatment of cognitive dysfunction, depression and anxiety observed in veterans of PGW-1.According to Bach Pharma's website, "Bach has identified and licensed a lead candidate, monosodium α-luminol (GVT®), a phthalazinedione formulation that acts by reversing oxidative stress and by serving as a buffer to restore and maintain redox homeostasis."
Earlier CDMRP-funded studies have found that oxidative stress -- a form of cellular dysfunction involving the cells' mitochondria -- appears to be a core component of Gulf War Illness's disease manifestation. CoQ10 has been found in an early study to help, and CoQ10 combined with in a "mitochondrial cocktail," as well as other potential treatments, are currently under CDMRP-funded investigation.
**The full Bach Pharma press release is below.**
SOURCE: Bach Pharma Press Release