Description

We plan to use flupirtine, an approved drug that has been shown to improve cognition, learning and memory, and diminish muscular pain, in an animal model for the Persian Gulf War illnesses (GWI). Between the invasion of Kuwait by Iraq on August 2, 1990, and March 1991, the United States had 697,000 military personnel who participated in the air, sea, and ground war in the Persian Gulf region. During the war, service personnel were concurrently exposed to biological, chemical, and psychological environments. Upon their return, approximately 100,000 veterans have had unexplained complaints including loss of memory, difficulty concentrating, forgetfulness, headache, chronic fatigue, muscle and joint pain, ataxia, respiratory difficulties, and irritability.

Our proposed studies aim at investigating the protection and/or treatment of cognitive impairment and muscle weakness, the two hallmarks of the GWI. Rats will be treated daily for 60 days with dermal doses of 40 mg/kg DEET and 0.13 mg/kg permethrin, the same doses that American military personnel were exposed to during the Persian Gulf War; an animal model for GWI that we previously developed. We plan to use two daily doses of flupirtine, 5 and 10 mg/kg, that are comparable to the daily doses used by patients, in two paradigms: (1) Concurrently with DEET and permethrin for 60 days to protect against GWI, and (2) to treat this neurodegenerative disorder after the end of 60-day period treatment with DEET/permethrin for an additional 60 days. Twenty-four hours after the last dose, animals will be evaluated for neurological deficits by determining: clinical signs, sensorimotor and cognition functions, oxidative stress, apoptosis, and neuronal and glial cell morphology.

Ultimate Applicability of the Research

Type of Patients: Flupirtine is an approved drug that has been used for treatment of patients with memory and sensorimotor deficits, the major complaints veterans of the Gulf War. Thus, this drug would be a suitable treatment for this segment of the population.

The Potential Clinical Application, Benefit and Risks: Previous studies have proven flupirtine to be very effective in the treatment of memory and sensorimotor deficits. The finding that flupirtine is safe with few side effects and does not induce dependence or tolerance, makes this drug an attractive and clinically safe drug to treat those veterans with GWI.

Contribution of This Study to Advancing the Field of GWI Research: The results of the proposed studies should greatly contribute to advancing our knowledge in the treatment of GWI. Improvement of cognition and sensorimotor function of Gulf War veterans should result in improvement of their quality of life.