Radiation Countermeasures (USUHS)
Abstract
Radiation Countermeasures (USUHS/AFRRI): For the Uniformed Services University of the Health Sciences/Armed Forces Radiobiology Research Institute (USUHS/AFRRI), this program supports developmental, mission directed research to investigate new concepts and approaches that will lead to advancements in biomedical strategies for preventing and treating the health effects of human exposure to ionizing radiation as well as radiation combined with injuries (burns, wounds, hemorrhage, microbiome, gastrointestinal damage, neurobehavioral deficits, bone marrow damage), termed radiation combined injury (RCI). RCI’s were observed at Hiroshima and Nagasaki, Japan, where 60-70% of victims received thermal burns concurrent with radiation injury. At the Chernobyl reactor meltdown, 10% of 237 victims exposed to radiation received thermal burns as well. In animal models of RCI including rat, guinea pig, dog, and swine, burns and wounds usually increase mortality after otherwise non-lethal radiation exposures. Consequences of RCI include acute myelosuppression, immune system inhibition, fluid imbalance, macro/microcirculation failure, massive cellular damage, and disruption of vital organ functions, which can lead to multiple organ dysfunction syndrome. There are different syndromes based on the time of manifestation in relation to radiation exposure; acute, delayed, late, and chronic syndromes. Acute radiation syndrome (ARS) is characterized by the differential response of the important organs to different doses of radiation. The ARS sub-syndromes include three major clinically-relevant pathologies; hematopoietic sub-syndrome (H-ARS), gastrointestinal sub-syndrome (GI-ARS), and neurovascular sub-syndrome (NV-ARS or CNS-ARS). Radiation countermeasures have been categorized as radioprotectors, radiomitigators, and therapeutics, based on the time of administration in relation to radiation exposure. The majority of countermeasures developed are for specific tissue injuries or specific syndromes. ARS is receiving the most attention, though other syndromes also need equal consideration. Currently, treatments for ARS are limited: only the H-ARS has viable therapeutic options and even those are limited; Neupogen, Neulasta, Leukine, and Nplate. USUHS/AFRRI researchers made significant contributions in the initial development of the first three agents. These H-ARS treatments are genetically engineered recombinant growth factors or cytokines that were developed for other indications and recently repurposed for H-ARS. All U.S. Food and Drug Administration (FDA) -approved agents for H-ARS are radiomitigators. No radioprotector, either for H-ARS or GI-ARS has yet been approved for human use. Due to the increasing risk of nuclear and radiological terrorist attacks or accidents has renewed interest in developing radiation medical countermeasures. Our Radiation Countermeasures goals ranges from exploration of biological processes likely to form the basis of technological solutions, to initial feasibility studies of promising solutions. Program objectives focus on preventing and mitigating the health consequences from exposures to ionizing radiation, in the context of probable threats to U.S. forces in current tactical, humanitarian and counterterrorism mission environments. New protective, and/or combination of FDA approved treatments and therapeutic strategies will broaden the military commander's options for operating within nuclear or radiological environments by minimizing both short-and long-term risks of adverse health consequences. Research findings are focused to advance the understanding and to produce the following: (1) To identify new therapeutics candidates that show promising advancement to further development; (2) To developed novel technologies to minimized the use of animal models in the study of radiation countermeasure effects; (3) To investigate the overall radiation effect by countermeasures in the microbiome and anatomical tissue; (4) To find novel biomarkers, late effects and immunosuppression of radiation injury that can quantitate effects on combat performance decrements; (4) To identify novel therapeutic strategies that will support military operations within a nuclear or radiological environment minimizing ground troops short and long term adverse risk.
Document Details
- Document Type
- Project
- Publication Date
- Oct 01, 2023
- Source ID
- 241C_0602787DHA_2_0130_PB_2023
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