Nonhuman primates as models for the discovery and development of radiation countermeasures

Abstract

Introduction Despite significant scientific advances over the past six decades toward the development of safe and effective radiation countermeasures for humans using animal models, only two pharmaceutical agents have been approved by United States Food and Drug Administration (US FDA) for hematopoietic acute radiation syndrome (H-ARS). Additional research efforts are needed to further develop large animal models for improving the prediction of clinical safety and effectiveness of radiation countermeasures for ARS and delayed effects of acute radiation exposure (DEARE) in humans. Area covered The authors review the suitability of animal models for the development of radiation countermeasures for ARS following the FDA Animal Rule with a special focus on nonhuman primate (NHP) models of ARS. There are seven centers in the United States currently conducting studies with irradiated NHPs, with the majority of studies being conducted with rhesus monkeys. Expert opinion The NHP model is considered the gold standard animal model for drug development and approval by the FDA. The lack of suitable substitutes to NHP models for predicting response in humans serves as a bottleneck for the development of radiation countermeasures. Additional large animal models need to be characterized to support the development and FDA-approval of new radiation countermeasures.

Changes in the Gut Microbiome Community of nonhuman primate following radiation injury

“…Despite the signi cant clinical incidence of intestinal radiation injury in cancer patients, effective therapies to address intestinal radiation injury are not available. NHPs seem to reproduce several aspects of acute radiation syndrome (ARS) observed in humans (Reviewed in [20]). In light of similarity to physiological responses to radiation in humans, evolutionary relatedness, similarity in organ structure; GI symptoms and metabolism to humans, NHPs are considered to be the benchmark animal model for studying ARS.…”

Changes in the Gut Microbiome Community of Nonhuman Primate Following Radiation Injury

“…Despite the signi cant clinical incidence of intestinal radiation injury in cancer patients, effective therapies to address intestinal radiation injury are not available. NHPs seem to reproduce several aspects of acute radiation syndrome (ARS) observed in humans (Reviewed in [13]). In light of similarity to physiological responses to radiation in humans, evolutionary relatedness, similarity in organ structure; GI symptoms and metabolism to humans, NHPs are considered to be the benchmark animal model for studying ARS.…”

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status

“…GT3 has been investigated for its radioprotective efficacy against 60 Co c-irradiation using an NHP model with encouraging results (Singh et al 2016b;Singh & Olabisi 2017). GT3 helped the recovery of radiation-induced thrombocytopenia and neutropenia compared to the vehicle controls; these results were especially significant after lethal exposures to 5.8 or 6.5 Gy 60 Co c-TBI.…”