Scientific Background
When a radioactive atom decays, it releases radiation. Radiation released from radioactive material is ionizing, which means that it can strip electrons from compounds with which it interacts, including living tissue. This can lead to serious injuries to different organ systems, and even death. The effects of external radiation on the body may appear within minutes (acute radiation syndrome) or develop many years after exposure (delayed effects of acute radiation exposure). In general, exposure to higher doses of radiation produce symptoms more rapidly.
Strategic Planning
The approach to the strategic planning process used to develop the NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Radiological and Nuclear Threats, released in 2005, was to identify the critical gaps in knowledge and capabilities, and then to set goals for the development of medical countermeasures that could be broadly applied in many situations. Progress made in achieving these goals was provided in 2012, with the publication of the Strategic Plan and Research Agenda for Medical Countermeasures against Radiological and Nuclear Threats Progress Report: 2005-2011 and Future Directions: 2012-2016.
Basic and Translational Research
The creation and acquisition of new and effective medical countermeasures for radiation injuries among the civilian population will require basic research to expand the knowledge base, as well as translational research to begin the transformation of fundamental knowledge gained into product development.
Focused Product Development
Some currently-available drugs as well as approaches undergoing testing in pre-clinical models of radiation injury have shown great promise as mitigators/treatments, improving survival and enhancing other indicators such as levels of immune and other blood cells.
In fact, in 2015, label-extensions were granted by the United States Food and Drug Administration (FDA) for the use of Neupogen® (filgrastim) and Neulasta® (pegfilgrastim) to treat casualties in the wake of a radiological or nuclear incident. These approvals have paved the way for use of these already-stockpiled drugs, without the need for an Emergency Use Authorization (EUA), and has elevated their use to an expected standard of care in a mass casualty, radiation public health emergency. This approval by the FDA was based on large animal efficacy protocols supported by NIAID funding. In those GLP studies, both growth factor-based drugs improved survival when administered 24 hours after radiation exposure.
The NIAID’s focus on product development makes the kinds of studies that resulted in these licensures available to companies and/or academic investigators who are developing drugs for a radiation indication. Activities have included independent confirmation of product efficacy in well-validated, small and large animal models of hematopoietic, gastrointestinal and lung syndromes resulting from radiation exposure; toxicological, pharmacological, and drug candidate synthesis/stability studies to gather data that can assist investigators in their applications for additional sources of funding; pivotal animal-model studies of efficacy; studies conducted under Good Laboratory Practices standards in small and large animal models as required by the FDA Animal Rule for product licensure; and additional studies to enable investigators to advance products toward FDA licensure.
Infrastructure for Research and Product Development
Since the program’s inception, the primary mechanism to support infrastructure enhancement has been the Centers for Medical Countermeasures Against Radiation Consortium (CMCRC), which has helped to expand both the physical and human infrastructure devoted to radiation countermeasures research. Initially awarded in 2005, the CMCRCs are now in their third iteration, with four current centers.
Centers for Medical Countermeasures Against Radiation Consortium
The Medical Countermeasures against Radiation Consortium (CMCRC) is a network of national research centers working together to develop effective and comprehensive medical countermeasures applicable to all subsets of the civilian population in the event of radiological or nuclear emergencies. They utilize multidisciplinary basic and translational research to support the development of new medical products that will assess, diagnose, mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological/nuclear terrorist event or accidental exposure. This research program was originally established by NIAID in 2005 under RFA-AI-04-045 and has been reissued three more times: 2010 (RFA-AI-09-036), 2015(RFA-AI-14-055), and 2020 (RFA-AI-19-012). Read more about Centers for Medical Countermeasures Against Radiation Consortium.