Animal Model Considerations for Medical Countermeasure Development for Radiation and Sulfur Mustard Exposures: Animal...

Development of medical countermeasures (MCM) to mitigate and/ or treat the pulmonary complications associated with exposure to chemical, radiological, and/ or nuclear weapons is a national, public health preparedness posture priority in the United States (US). Pulmonary exposure to either sulfur mustard vapor or radiation causes oxidative damage, vascular injury, hyperinflammation, and pro-fibrotic signaling cascades that lead to life-threatening and potentially debilitating lung disease. There is no MCM currently approved by the US Food and Drug Administration (FDA) to mitigate and/ or treat lung injury caused by sulfur mustard or radiation exposure. Thus, there remains a major unmet public health need for development of threat-agnostic, host-directed therapeutics that target common pathophysiological mechanisms underlying the progression of acute and/ or late lung injury independent of the etiology of disease. This review describes the clinical manifestations and underlying mechanisms of sulfur mustard and radiation-induced lung injury and regulatory considerations for MCM development under the non-traditional Animal Rule pathway.