RT Journal Article
SR Electronic
T1 Cracking the egg: Potential of the developing chicken as a model system for non-clinical safety studies of pharmaceuticals
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.115.227025
DO 10.1124/jpet.115.227025
A1 Sigrid Bjornstad
A1 Lars Peter Engeset Austdal
A1 Borghild Roald
A1 Joel Clinton Glover
A1 Ragnhild E Paulsen
YR 2015
UL http://jpet.aspetjournals.org/content/early/2015/10/07/jpet.115.227025.abstract
AB The advance of perinatal medicine has improved the survival of extremely premature babies, thereby creating a new and heterogeneous patient group with limited information on appropriate treatment regimens. The developing fetus and neonate have traditionally been ignored populations with regard to safety studies of drugs, making medication during pregnancy and of newborns a significant safety concern. Recent initiatives of the FDA and EMA have been passed with the objective of expanding the safe pharmacological treatment options in these patients. There is a consensus that neonates should be included in clinical trials. Prior to these trials, drug leads are tested in toxicity and pharmacology studies as governed by several guidelines summarized in the multidisciplinary ICH M3 (R2). Pharmacology studies must be performed in the major organ systems: cardiovascular, the respiratory and the CNS. The chicken embryo and fetus have features that make it a convenient animal model for non-clinical safety studies where effects on all these organ systems can be tested. The developing chicken is inexpensive, accessible and nutritionally self-sufficient with a short incubation time and is ideal for drug screening purposes. Other high throughput models have been implemented. However, many of these have limitations, including difficulty in mimicking natural tissue architecture and function (human stem cells) and obvious differences from mammals in the respiratory organ system and certain aspects of CNS development (C. elegans, zebrafish).This minireview outlines the potential and limitations of the developing chicken as an additional model for the early exploratory phase of development of new pharmaceuticals.