BBT-059, a promising medical countermeasure, protects multi-organ systems from acute and delayed effects of radiation exposure in pre-clinical animal model

Summary Sanchita P. Ghosh1, Gregory Holmes-Hampton1, George Cox2, and Vidya P. Kumar1. Background: The threat of nuclear exposure is heightened and there is unmet need to identify potential countermeasures for acute radiation syndrome (ARS). Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as well as to increase the overall prognosis of an exposed individual long term. Here we report BBT-059 (PEGylated IL-11 analog developed by Bolder Biotechnology), a promising prophylactic radiation countermeasure in mice, protect multi-organ systems exposed to total body radiation (TBI) or partial body irradiation (PBI), as well as delayed effects of acute radiation exposure (DEARE). Method: A single dose (0.3 mg/kg) of BBT-059 was tested in mice, injected at several time points from 24 h pre- to 24 h post-TBI.CBC, cytokines, bone marrow progenitor cells and gastrointestinal crypt cells were evaluated in irradiated mice. Mice were exposed to either total body Co-60 gamma radiation or partial body irradiation using the clinical linear accelerator (4MV X-rays).Animal were monitored up to one year following exposure and radiation-induced damage was evaluated in major organs. Results: BBT-059 significantly increased survival in mice exposed to supralethal doses of TBI, protected hematopoietic system(recovery of CBC, bone marrow CFU, markers of bone marrow aplasia EPO, TPO, FLt3L) as well as gastrointestinal (GI) system (recovery of viable crypts, reduction of bacterial translocation and sepsis markers SAA, PCT). A dose reduction factor of 1.28 was calculated for BBT-059 administered pre-TBI compared to saline. BBT-059 also demonstrated significantly higher survival in GI-ARS PBI model, protected crypts. In the long term study in surviving (6 and 12 months post-TBI) animals showed accelerated recovery of CBC, bone marrow CFU, sternal cellularity and megakaryocyte numbers in
RITM0040047
Background: The threat of nuclear exposure is heightened and there is unmet need to identify potential countermeasures for acute radiation syndrome (ARS). Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as well as to increase the overall prognosis of an exposed individual long term. Here we report BBT-059 (PEGylated IL-11 analog developed by Bolder Biotechnology), a promising prophylactic radiation countermeasure in mice, protect multi-organ systems exposed to total body radiation (TBI) or partial body irradiation (PBI), as well as delayed effects of acute radiation exposure (DEARE). Method: A single dose (0.3 mg/kg) of BBT-059 was tested in mice, injected at several time points from 24 h pre- to 24 h post-TBI.CBC, cytokines, bone marrow progenitor cells and gastrointestinal crypt cells were evaluated in irradiated mice. Mice were exposed to either total body Co-60 gamma radiation or partial body irradiation using the clinical linear accelerator (4MV X-rays).Animal were monitored up to one year following exposure and radiation-induced damage was evaluated in major organs. Results: BBT-059 significantly increased survival in mice exposed to supralethal doses of TBI, protected hematopoietic system(recovery of CBC, bone marrow CFU, markers of bone marrow aplasia EPO, TPO, FLt3L) as well as gastrointestinal (GI) system (recovery of viable crypts, reduction of bacterial translocation and sepsis markers SAA, PCT). A dose reduction factor of 1.28 was calculated for BBT-059 administered pre-TBI compared to saline. BBT-059 also demonstrated significantly higher survival in GI-ARS PBI model, protected crypts. In the long term study in surviving (6 and 12 months post-TBI) animals showed accelerated recovery of CBC, bone marrow CFU, sternal cellularity and megakaryocyte numbers in drug treated mice compared to control. In addition, increased senescence was observed