Development and Licensure of Medical Countermeasures to Treat Lung Damage Resulting from a Radiological or Nuclear Incident

Abstract

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.

A lipidomic and metabolomic serum signature from nonhuman primates exposed to ionizing radiation

“…While previous studies have reported radiation metabolic signatures in NHP urine at various time points (Johnson et al 2012; Pannkuk et al 2015), information on perturbations from IR in NHP serum is lacking, as only one targeted study exists (Jones et al 2014). These studies are needed to establish biodosimetry methodology in the event of large-scale radiological exposures (DiCarlo et al 2010;2012). …”

Global Metabolomic Identification of Long-Term Dose-Dependent Urinary Biomarkers in Nonhuman Primates Exposed to Ionizing Radiation

“…Due to increased terrorist threats and the most recent nuclear accident at the Fukushima Nuclear Power Plant, there has been an increasing awareness of, and need for, medical countermeasures to potential radiological and nuclear exposures (1, 2). One such need is the development of clinical and field-based diagnostic tools for biodosimetry and the determination of individual radiation exposure.…”

Triptolide mitigates radiation-induced pulmonary fibrosis via inhibition of axis of alveolar macrophages-NOXes-ROS-myofibroblasts

“…So far, there is no effective medication for it. 1 Clearly, an anti-fibrotic agent with a defined action mechanism is urgently needed. Our previous studies and others have shown that TPL, a diterpenoid epoxide purified from the Tripterygiumwilfordii Hook F, exhibits both anti-inflammation and anti-tumor activities.…”