The search for single or combined radiation countermeasures that mitigate the development of Acute Radiation Syndrome (ARS) after radiation exposure remains a prominent goal of the U.S. government. This study was undertaken to determine whether PrC-210 and G-CSF, when administered 24-48 h postirradiation, would confer an additive or synergistic survival benefit and mitigate ARS in mice that had received an otherwise 96% lethal radiation dose. Our results show that optimum systemic doses of PrC-210 and G-CSF, when administered 24 h or later after a 96% lethal dose of whole-body irradiation, conferred: 1. strong individual survival benefits (PrC-210 44%, P = 0.003), (G-CSF 48%, P = 0.0002), 2. a profound combined 85% survival benefit (P < 0.0001) when administered together, and on day 14 postirradiation, 3. peripheral white blood cell/lymphocyte counts equal to unirradiated controls, 4. dense bone marrow cell density (>65% of unirradiated controls), 5. jejunal villi density that equaled 90% of unirradiated controls, and 6. spleen weights that equaled 93% of unirradiated controls. Our results show that PrC-210 and G-CSF given together 24 h after irradiation confer strong additive efficacy by protecting the immune system, and enabling recovery of the bone marrow, and they work synergistically to enable recovery of peripheral white blood cells in circulating blood.
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October 2024
REGULAR ARTICLES|
October 08 2024
Significant Reduction of Radiation-Induced Death in Mice Treated with PrC-210 and G-CSF after Irradiation
William E. Fahl;
William E. Fahl
1
aObvia Pharmaceuticals Ltd., Madison, Wisconsin 53719
bWisconsin Institutes for Medical Research, McArdle Laboratory, University of Wisconsin-Madison, Madison, Wisconsin 53705
1Corresponding author: William E. Fahl, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53792; email: [email protected].
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Bryan L. Fahl;
Bryan L. Fahl
aObvia Pharmaceuticals Ltd., Madison, Wisconsin 53719
bWisconsin Institutes for Medical Research, McArdle Laboratory, University of Wisconsin-Madison, Madison, Wisconsin 53705
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Devin Schult;
Devin Schult
bWisconsin Institutes for Medical Research, McArdle Laboratory, University of Wisconsin-Madison, Madison, Wisconsin 53705
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Torsten R. Goesch
Torsten R. Goesch
aObvia Pharmaceuticals Ltd., Madison, Wisconsin 53719
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Radiat Res (2024) 202 (4): 662–669.
Article history
Received:
April 03 2024
Accepted:
July 08 2024
Citation
William E. Fahl, Bryan L. Fahl, Devin Schult, Torsten R. Goesch; Significant Reduction of Radiation-Induced Death in Mice Treated with PrC-210 and G-CSF after Irradiation. Radiat Res 1 October 2024; 202 (4): 662–669. doi: https://doi.org/10.1667/RADE-24-00102.1
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