Meeting Report: A Poly-Pharmacy Approach to Mitigate Acute Radiation Syndrome.

The National Institute of Allergy and Infectious Diseases, Radiation and Nuclear Countermeasures Program, was tasked by the United States Congress and the U.S. Department of Health and Human Services to identify and fund early-to-mid-stage development of medical countermeasures (MCMs) to treat radiation-induced injuries. In developing MCMs to treat various sub-syndromes (e.g., hematopoietic, gastrointestinal, lung), it is important to investigate whether a poly-pharmacy approach (i.e., drug cocktails) can provide additive benefits to mitigate injuries arising from the acute radiation syndrome (ARS). In addition, potential drug-drug interactions must be examined. For this reason, a workshop was held, which centered on understanding the current state of research investigating poly-pharmacy approaches to treat radiation injuries. The first session set the stage with an introduction to the concept of operations or support available for the response to a nuclear incident, as this is the key to any emergency response, including MCM availability and distribution. The second session followed the natural history of ARS in both humans and animal models to underscore the complexity of ARS and why a poly-pharmacy approach may be necessary. The third session featured talks from investigators conducting current MCM poly-pharmacy research. The meeting closed with a focus on regulatory considerations for the development of poly-pharmacy approaches or combination treatments for ARS.

Use of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health Emergency.

In response to concerns over possible radiological or nuclear incidents, the Radiation and Nuclear Countermeasures Program within the National Institute of Allergy and Infectious Diseases (NIAID) was tasked by the U.S. Department of Health and Human Services to support development of medical countermeasures (MCM) to treat the acute and delayed injuries that can result from radiation exposure. To date, the only three drugs approved by the U.S. Food and Drug Administration for treatment of acute radiation syndrome are growth factors targeting granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages. Although these are currently stockpiled for deployment in response to a mass casualty scenario, these growth factors will likely be administered in a scarce-resources environment and availability may be limited. Therefore, there is growing interest in understanding the role that these growth factors play in mitigating radiation damage, to optimize their use and maximize the number of people who can be treated. For these reasons, the NIAID and the Radiation Injury Treatment Network organized a workshop to explore the use of growth factors and other cytokines as MCMs in the treatment of radiation-induced injuries. Subject matter experts from government, industry and academia gathered at this workshop to discuss the concept of operations, triage and treatment, administration to diverse civilian populations, growth factors under development for radiation indications, and how the practice of medicine can inform other potential approaches.

Use of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency.

Due to the threat of a radiological or nuclear incident that could impact citizens, the U.S. Department of Health and Human Services tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early- to mid-stage medical countermeasure (MCM) development to treat radiation-induced injuries. Given that the body's natural response to radiation exposure includes production of growth factors and cytokines, and that the only drugs approved by the U.S. Food and Drug Administration to treat acute radiation syndrome are growth factors targeting either the granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages, there is interest in understanding the role that these factors play in responding to and/or ameliorating radiation damage. Furthermore, in an environment where resources are scarce, such as what might be expected during a radiation public health emergency, availability of growth factor or other treatments may be limited. For these reasons, the NIAID partnered with the Radiation Injury Treatment Network (RITN), whose membership includes medical centers with expertise in the management of bone marrow failure, to explore the use of growth factors and other cytokines as MCMs to mitigate/treat radiation injuries. A workshop was convened that included government, industry and academic subject matter experts, with presentations covering the anticipated concept of operations during a mass casualty incident including triage and treatment, growth factors under development for a radiation indication, and how the practice of medicine can inform other potential approaches, as well as considerations for administration of these products to diverse civilian populations. This report reviews the information presented, and provides an overview of the discussions from a guided breakout session.