Radiation Countermeasures (USUHS)
Abstract
For the Uniformed Services University of the Health Sciences (USU), 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), termed combined injury (CI). Research 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 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. FY 2019 Accomplishments: - Reported translational research findings on Ghrelin therapy for mitigation of small intestine injury by sustaining granulocyte-colony stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and macrophage inflammatory protein 1-alpha (MIP-1α), and decreased interleukin-18 (IL-18) in small intestine after combined radiation injury (CI). Ghrelin mitigating small intestinal injury induced by CI was confirmed by histology examination and reduction of cell death biomarker in small intestine. - Reported research findings on radiation injury (RI) and CI induced brain hemorrhage in cerebrum and cerebellum by reducing circulating platelets and brain energy production and increasing brain inflammation and cell death signals, - Demonstrated in an animal model that combinational therapy of Ghrelin and Neulasta inhibited brain hemorrhage from RI and CI by recovering energy production, inhibiting inflammation, and blocking cell death signals in brain as well as increasing platelets in circulation. -Reported animal test/evaluation findings on radiation drug candidate, BBT-059, developed by Bolder Biotechnology, protected mice from radiation-induced gastro-intestinal injury, significantly increased serum citrulline, reduced inflammatory serum amyloid A (SAA) levels and bacterial translocation in liver and spleen. In addition, research findings showed that animals treated with BBT-059 survived up to 12 months post-radiation exposure from lethal and supra-lethal dose (delayed effects of acute radiation exposure, DEARE) with no histological changes in major organs including heart, kidney, brain, and liver. -Reported animal test/evaluation findings on radiation drug candidate, PLX-R18, developed by Pluristem Therapeutics, demonstrated significant increase in 30-day survival when it was administered two doses on day 1 pre and day 3 post-radiation. In addition, research findings showed that PLX-R18 protected mice from radiation induced hematopoietic acute radiation syndrome, significantly accelerated recovery of peripheral blood and bone marrow progenitor cells. - Completed animal test toxicity study of IL-18BP as a putative radiation drug and found no toxicity after subcutaneous (SC) injection from 0.25 mg/kg to 5.0 mg/kg to CD2F1 mice. - Demonstrated that a single injection of rhIL-18BP (1.5mg/kg) to mice at 24 h, 48 or 72 h post-total-body irradiation (TBI) exhibited a delayed mortality time in comparison with vehicle control-treated mice. In addition, IL-18BP (1.5 mg/kg, 48 h post-radiation) significantly increased bone marrow hematopoietic stem and progenitor cell clonogenicity and blood platelet number in mice after 9 or 10 Gy (LD70/30 and LD90/30) TBI. Also, two doses injection of rhIL-18BP (1.5mg/kg) to mice at 48 h and 5 days post-9 Gy TBI significantly increased 30-day survival of mice in compression of vehicle-control injected and irradiated mice. -Completed studies on the radiation-dependent effects on the human HSC proteome by in vitro methods; a few but promising radiation-induced protein biomarkers have been identified. -Generated additional translational information on radiation-induced biomarker signature using samples obtained from irradiated large animal model. This work is being done using transcriptomics and metabolomics/lipidomics platforms. -Successfully initiated a radiation induced microbiome study using irradiated murine model samples This work will continue by using bacterial DNA analysis as well as metabolomics/lipidomics.
Document Details
- Document Type
- Accomplishment
- Publication Date
- Oct 01, 2021
- Source ID
- de4a8010532f9ef2dcd05872bbb0964d