@article{0e0d2894eee646b5ba8456d655935b7a,
title = "Mitigation of total body irradiation-induced mortality and hematopoietic injury of mice by a thrombopoietin mimetic (JNJ-26366821)",
abstract = "The threat of a nuclear attack has increased in recent years highlighting the benefit of developing additional therapies for the treatment of victims suffering from Acute Radiation Syndrome (ARS). In this work, we evaluated the impact of a PEGylated thrombopoietin mimetic peptide, JNJ-26366821, on the mortality and hematopoietic effects associated with ARS in mice exposed to lethal doses of total body irradiation (TBI). JNJ-26366821 was efficacious as a mitigator of mortality and thrombocytopenia associated with ARS in both CD2F1 and C57BL/6 mice exposed to TBI from a cobalt-60 gamma-ray source. Single administration of doses ranging from 0.3 to 1 mg/kg, given 4, 8, 12 or 24 h post-TBI (LD70 dose) increased survival by 30–90% as compared to saline control treatment. At the conclusion of the 30-day study, significant increases in bone marrow colony forming units and megakaryocytes were observed in animals administered JNJ-26366821 compared to those administered saline. In addition, enhanced recovery of FLT3-L levels was observed in JNJ-26366821-treated animals. Probit analysis of survival in the JNJ-26366821- and saline-treated cohorts revealed a dose reduction factor of 1.113 and significant increases in survival for up to 6 months following irradiation. These results support the potential use of JNJ-26366821 as a medical countermeasure for treatment of acute TBI exposure in case of a radiological/nuclear event when administered from 4 to 24 h post-TBI.",
author = "Kumar, {Vidya P.} and Holmes-Hampton, {Gregory P.} and Shukla Biswas and Sasha Stone and Sharma, {Neel Kamal} and Bernadette Hritzo and Mary Guilfoyle and Gary Eichenbaum and Chandan Guha and Ghosh, {Sanchita P.}",
note = "Funding Information: The authors gratefully acknowledge Kefale Wuddie, Zemenu Aschenake, HM1 Paul O{\textquoteright}Brien, and Fialka G. Ward for technical assistance. The authors also would like to thank Dr. Carmen Rios and Dr. Merriline Satyamitra for their contributions in the scientific discussion and intellectual input. Support for the work was provided by grants from the National Institute of Allergy and Infectious Diseases (AA112044-001-04000 to SG and 1U01AI133608-01 to SG), JPC-7 project DM178020, and the AFRRI Intramural funding RAB23338. The opinions contained herein are the private views of the authors, and are not necessarily those of Armed Forces Radiobiology Research Institute, the Uniformed Services of the University of the Health Sciences, or the Department of Defense. Funding Information: The authors gratefully acknowledge Kefale Wuddie, Zemenu Aschenake, HM1 Paul O?Brien, and Fialka G. Ward for technical assistance. The authors also would like to thank Dr. Carmen Rios and Dr. Merriline Satyamitra for their contributions in the scientific discussion and intellectual input. Support for the work was provided by grants from the National Institute of Allergy and Infectious Diseases (AA112044-001-04000 to SG and 1U01AI133608-01 to SG), JPC-7 project DM178020, and the AFRRI Intramural funding RAB23338. The opinions contained herein are the private views of the authors, and are not necessarily those of Armed Forces Radiobiology Research Institute, the Uniformed Services of the University of the Health Sciences, or the Department of Defense. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41598-022-07426-7",
language = "English (US)",
volume = "12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}