Animal models for acute radiation syndrome drug discovery

Abstract

Introduction: Although significant scientific advances have been made over the past six decades in developing safe, nontoxic and effective radiation/medical countermeasures (MCMs) for acute radiation syndrome (ARS), no drug has been approved by the US FDA. The availability of adequate animal models is a prime requisite under the criteria established by the FDA ‘animal rule’ for the development of novel MCMs for ARS and the discovery of biomarkers for radiation exposure.

Areas covered: This article reviews the developments of MCMs to combat ARS, with particular reference to the various animal models (rodents: mouse and rat; canine: beagle; minipigs and nonhuman primates [NHPs]) utilized for the in-depth evaluation. The objective, pathways and challenges of the FDA Animal Efficacy Rule are also discussed.

Expert opinion: There are a number of well-defined animal models, the mouse, canine and NHP, that are being used for the development of MCMs. Additional animal models, such as the minipig, are under development to further assist in the identification, efficacy testing and approval of MCMs under the FDA Animal Efficacy Rule.

Keywords:

• animal model
• canine
• FDA Animal Efficacy Rule
• medical countermeasures
• mice
• minipig
• nonhuman primate

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Erratum

Acknowledgments

The authors are thankful to Col. L Andrew Huff and Captain David Lesser for helpful discussions. The opinions or assertions contained herein are the professional views of the authors and are not necessarily those of the Department of Defense, USA. Mention of specific therapeutic agents does not constitute endorsement by the US Department of Defense, and trade names are used only for the purpose of clarification. The authors express appreciation to Stephen Y Wise and Oluseyi O Fatanmi for outstanding photomicrography support. The authors apologize to those having contributed substantially to the topics discussed herein that they were unable to cite because of space constraints.

Declaration of interest

VK Singh is employee of the US Department of the Defense. Furthermore, VL Newman and AN Berg are affiliated with the Armed Forces Radiobiology Research Institute, a US Department of Defense research laboratory, as research project staff. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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