The benefits, limitations and opportunities of preclinical models for neonatal drug development

Abstract

Increased research to improve preclinical models to inform the development of therapeutics for neonatal diseases is an area of great need. This article reviews five common neonatal diseases - bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, perinatal hypoxic-ischemicencephalopathyand neonatal sepsis - and the available in vivo, in vitro and in silico preclinicalmodels for studying these diseases. Better understanding of the strengths and weaknesses of specialized neonatal disease models will help to improve their utility,may add to the understanding of themode of action and efficacy of a therapeutic, and/ormay improve the understanding of the disease pathology to aid in identification of new therapeutic targets. Although the diseases covered in this article are diverse and require specificapproaches, several high-level, overarching key lessons can be learned by evaluating the strengths, weaknesses and gaps in the available models. This Review is intended to help guide current and future researchers toward successful development of therapeutics in these areas of high unmet medical need.