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Due to the ever-present threat of a radiological or nuclear accident or attack, the National Institute of Allergy and Infectious Diseases, Radiation Medical Countermeasures Program was initiated in 2004. Since that time, the Program has funded research to establish small and large animal models for radiation damage, as well as the development of approaches to mitigate/treat normal tissue damage following radiation exposure. Because some of these exposures may be high-dose, and yet heterogeneous, the expectation is that some victims will survive initial acute radiation syndromes (e.g. hematopoietic and gastrointestinal), but then suffer from potentially lethal lung complications. For this reason, efforts have concentrated on the development of animal models of lung irradiation damage that mimic expected exposure scenarios, as well as drugs to treat radiation-induced late lung sequelae including pneumonitis and fibrosis. Approaches targeting several pathways are under study, with the eventual goal of licensure by the United States Food and Drug Administration for government stockpiling. This Commentary outlines the status of countermeasure development in this area and provides information on the specifics of licensure requirements, as well as guidance and a discussion of challenges involved in developing and licensing drugs and treatments specific to a radiation lung damage indication. [ABSTRACT FROM AUTHOR]

More than 50 years after the Apollo missions ended, the National Aeronautical and Space Administration (NASA) and other international space agencies are preparing a return to the moon as a step towards deep space exploration. At doses ranging from a fraction of a Gray (Gy) to a few Gy, crew will be at risk for developing bone marrow failure associated with the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) requiring pharmacological intervention to reduce risk to life and mission completion. Four medical countermeasures (MCM) in the colony stimulating factor class of drugs are now approved for treatment of myelosuppression associated with ARS. When taken in conjunction with antibiotics, fluids, antidiarrheals, antiemetics, antipyretics, and other treatments for symptomatic illness, the likelihood for recovery and mission completion can be greatly improved. The current review describes the performance and health risks of deep space flight, ionizing radiation exposure during crewed missions to the moon and Mars, and U.S. Food and Drug Administration (FDA)-approved medical interventions to treat ARS. With an expansion of human exploration missions beyond low Earth orbit (LEO), including near-term Lunar and future Mars missions, inclusion of MCMs to counteract ARS in the spaceflight kit will be critical for preserving crew health and performance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Isabel L. Jackson is a consultant for Partner Therapeutics, the manufacturer of Leukine®. All other authors declare they have no known competing financial interests or personal relationships that could have appeared, (Copyright © 2022. Published by Elsevier B.V.)

The purpose of preclinical murine model development is to establish that the pathophysiological outcome of the rodent model of radiation-induced lung injury is sufficiently representative of the anticipated pulmonary response in the human population. This objective is based on concerns that the C57BL/6J strain may not be the most appropriate preclinical model of lethal radiation lung injury in humans. In this study, the authors assessed this issue by evaluating the relationship between morbidity (pulmonary function, histopathologic damage) and mortality among three strains of mice: C57BL/6J, CBA/J, and C57L/J. These different strains display variations in latency and phenotypic expression of radiation-induced lung damage. By comparing the response of each strain to the human pulmonary response, an appropriate animal model(s) of human radiation-induced pulmonary injury was established. Observations in the C57L/J and CBA/J murine models can be extrapolated to the human lung for evaluation of the mechanisms of action of radiation as well as future efficacy testing and approving agents that fall under the "Animal Rule" of the U.S. Food and Drug Administration (FDA) (21 CFR Parts 314 and 601).