The National Institutes of Health (NIH) has recently awarded a five-year renewal, $13 million grant to National Jewish Health and the University of Colorado Denver, both located in Denver, Colorado. This Center of Excellence was developed to focus on sulfur mustard toxicity in the lung and skin. The long-term goal of the Center is to develop an effective treatment for mustard gas-induced injury in lung and skin to treat sulfur mustard poisoning, a potent chemical warfare vesicant.
The collaborative studies are contained in three basic and translational projects and an Exposure Core is based both at National Jewish Health and the University of Colorado Denver. Analytical cores are based at both institutions. Administrative and Educational Cores are based at National Jewish Health.
Members of the Center are establishing optimal compounds, route and mode of delivery and research projects are ongoing to determine countermeasures that will help establish specific interventions needed to treat mustard gas-induced injury.
The Center members include the overall director Carl W. White, MD, National Jewish Health; Brian J. Day, PhD, project investigator at National Jewish Health; Rajesh Agarwal, PhD, project investigator and Exposure Core co-director at University of Colorado Denver.
Goal of the Counter Act Program
Develop new therapeutic measures to enhance our medical response capabilities in the event of an emergency, specifically sulfur mustard poisoning resulting in acute lung and skin injury.
Scope of Research
The research is based on animal models and in vitro (tissue culture) models of human primary lung and skin epithelial cells, and cell lines, and preclinical establishment of the most effective preventive and rescue therapies. After establishment of the models, efficacy testing of three classes of antioxidants has been initiated in each system (lung and skin; in vitro and in vivo). Therapeutic benefit is assessed through clinical and biological endpoints. Testing of combination therapies also is now underway in some of the projects. Efficacy testing currently is done in acute models of skin and lung injury using 2-chloroethyl-ethylsulfide (CEES; half-mustard).
Subsequent goals will include establishment of a model of chronic lung injury and skin injury, and, ultimately, to evaluate the most effective therapies in models of skin and lung injury due to full sulfur mustard (“mustard gas”). The developments of both preventive agents for use in first-responders, and of antidotes to minimize or reverse established sulfur mustard toxicity, are goals of this project.
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