Neuroscientists win DOD grant to help veterans with Gulf War illness

Neurosteroid to be tested for effectiveness
October 30, 2019

Many Gulf War veterans across the country are unable to escape chronic reminders of their time in combat. Specifically, 25 to 32 percent—or about 175,000 to 224,000 Gulf War veterans—are suffering from Gulf War illness (GWI). GWI causes unexplained cognitive difficulties, fatigue, gastrointestinal problems, respiratory symptoms, chronic headache, insomnia and widespread pain. There is an urgent need to develop therapeutic pharmaceuticals for those suffering from GWI, because they currently have no targeted treatment options.

Researchers from the Texas A&M College of Medicine have teamed up with the U.S. Department of Defense (DOD) to serve military members who have served our country. D. Samba Reddy, PhD, RPh, professor of neuroscience and experimental therapeutics at the College of Medicine, was recently awarded a grant from the Department of the Army for $342,000 over two years to conduct research on neurosteroid therapy for GWI.

The Gulf War, which lasted from 1990 to 1991 under President George H.W. Bush, was started when Iraq invaded and annexed Kuwait. Roughly 700,000 U.S. personnel were deployed as part of coalition troops. Combat started in January 1991 with a six week-long air and naval attack by the U.S. and its allies on targets within Iraq. In February of 1991, the coalition troops took their combat to the ground, where they were victorious against the Iraqi forces.

During combat, U.S. soldiers were exposed to numerous chemicals, including pyridostigmine bromide (PB), an oral pill taken as a prophylactic measure in case of a nerve agent attack. They were also exposed to N,N-diethyl-m-toluamide (DEET) and permethrin (PM), which were agents applied to the skin to protect soldiers from mosquito-borne diseases. Shortly after returning home, many of the soldiers who had been in combat started experiencing unexplained symptoms and illnesses that could not be properly diagnosed by existing medical diagnoses or laboratory tests.

“Basically, we hypothesize that GWI patients may have relatively low levels of neurosteroids in the brain due to exposure to chronic stress and chemical agents, including PB, DEET, and PM during the Gulf War,” Reddy said. “Low levels of neurosteroids means that there is a low level of tonic inhibition in the brain, which ultimately means that the brain is hyper-excitable and may be firing and sending messages to various areas of the body when it shouldn’t be.”

Reddy and his team have proposed a unique therapy that would use a synthetic neurosteroid, ganaxolone, which is currently undergoing clinical trials by the U.S. Food and Drug Administration (FDA). This treatment, combined with noninvasive neuroimaging using MRI, is an innovative therapy that can be rapidly applied to human clinical trials to offer relief to veterans with GWI. Since neurosteroids reduce GWI hallmark features of peripheral pain, central inflammation, neuronal tonic excitability and neurodegeneration, ganaxolone can be very effective in mitigating GWI symptoms.

Reddy will collaborate with Ashok Shetty, PhD, professor of molecular and cellular medicine. Shetty has developed a model of GWI that will help in testing the neurosteroid. His previous research has focused on addressing the neuroinflammation associated with the condition.

“Neurosteroids have been shown to be powerful neuroprotectants,” Reddy said. “The proposed therapy is uniquely broad spectrum towards GWI and is also based on our proven results from a previous chemical agent project. I am looking forward to the opportunity to give back to the military community through this new research project.”

Article written by Sarah Elmer

— Christina Sumners