Military medicine · 2025
Prophylactic Administration of BIO 300, A Radiation Medical Countermeasure, Improves Erythrocyte-Associated Parameters in the Rhesus Macaque Model.
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Fatanmi Oluseyi O, Wise Stephen Y, Petrus Sarah A, Melendez-Miranda Issa, Carpenter Alana D, Olson Hannah M, Serebrenik Artur A, Lugo-Roman Luis A, Kaytor Michael D, Singh Vijay K
Аннотация
INTRODUCTION: Exposure to ionizing radiation results in various subsyndromes of acute radiation syndrome, including the hematopoietic subsyndrome. Currently, there are no Food and Drug Administration approved drugs to protect from ionizing radiation exposure when administered prophylactically. Genistein, a soy isoflavone, has been implicated as a potent radioprotector. However, because of its poor bioavailability, it has not been developed into a medical countermeasure. To overcome this, an aqueous nanosuspension of synthetic genistein nanoparticles (BIO 300) has been developed. This study investigated the radioprotective efficacy of BIO 300 Injectable Suspension (BIO 300 IS) in a nonhuman primate (NHP) model of total-body irradiation (TBI).
MATERIALS AND METHODS: Eight rhesus macaques aged 8-14 years and weighing 10.75-25.1 kg were utilized in this study. Four were dosed intramuscularly (im) with BIO 300 IS (50 mg/kg) and 4 were dosed im with vehicle 24 hours before exposure to 5.8 Gy total-body radiation. Animals were monitored for survival and clinical observations for 60 days post-TBI. All animals underwent necropsy following euthanasia and tissues were collected for histopathology. Whole blood and serum were collected to analyze complete blood counts and blood biochemistry, respectively.
RESULTS: Of the 4 animals treated with BIO 300 IS, 3 survived through the 60-day study whereas only 2 of the 4 animals treated with vehicle survived. BIO 300 IS-treated animals had higher nadirs and/or faster recovery post-nadir for neutrophils, platelets, red blood cells, hemoglobin, and hematocrit. No difference in white blood cell counts were observed between BIO 300 IS- and vehicle-treated animals. Histopathological analysis revealed that BIO 300 IS-treated animals exhibited less hemorrhage, bone marrow atrophy, and gut associated lymphoid tissue depletion.
CONCLUSION: The data presented here suggest that BIO 300 IS radioprotective efficacy is mediated by improving red blood cell and platelet counts while also reducing adverse histopathological findings in NHPs undergoing TBI. These results suggest a potential novel mechanism of action for BIO 300 involving the protection of the megakaryocyte-erythropoietic progenitor population.
MATERIALS AND METHODS: Eight rhesus macaques aged 8-14 years and weighing 10.75-25.1 kg were utilized in this study. Four were dosed intramuscularly (im) with BIO 300 IS (50 mg/kg) and 4 were dosed im with vehicle 24 hours before exposure to 5.8 Gy total-body radiation. Animals were monitored for survival and clinical observations for 60 days post-TBI. All animals underwent necropsy following euthanasia and tissues were collected for histopathology. Whole blood and serum were collected to analyze complete blood counts and blood biochemistry, respectively.
RESULTS: Of the 4 animals treated with BIO 300 IS, 3 survived through the 60-day study whereas only 2 of the 4 animals treated with vehicle survived. BIO 300 IS-treated animals had higher nadirs and/or faster recovery post-nadir for neutrophils, platelets, red blood cells, hemoglobin, and hematocrit. No difference in white blood cell counts were observed between BIO 300 IS- and vehicle-treated animals. Histopathological analysis revealed that BIO 300 IS-treated animals exhibited less hemorrhage, bone marrow atrophy, and gut associated lymphoid tissue depletion.
CONCLUSION: The data presented here suggest that BIO 300 IS radioprotective efficacy is mediated by improving red blood cell and platelet counts while also reducing adverse histopathological findings in NHPs undergoing TBI. These results suggest a potential novel mechanism of action for BIO 300 involving the protection of the megakaryocyte-erythropoietic progenitor population.