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

Karen Davis-Bruno, Connie Chen, Vijay Urmaliya, Susan Laffan, Suna Seo, Stephanie Kourula, Lutz Wiesner, Luc De Schaepdrijver, LaRonda Morford, Karen Van Malderen, Sarah Campion, Julia Hui, Georg Schmitt, Fabrizio Salomone, Fabrizio Facchinetti, David Joseph, Costanza Casiraghi, Belinda Hayes, Amy Inselman

Journal: Disease models & mechanisms 2022;15(4):dmm049065

PMID: 35466995

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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-ischemic encephalopathy and neonatal sepsis - and the available in vivo, in vitro and in silico preclinical models 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 the mode of action and efficacy of a therapeutic, and/or may 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 specific approaches, 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.

Address: Pfizer Worldwide Research, Development, and Medical, Groton, CT 06340, USA.; U.S. Food and Drug Administration, National Center for Toxicological Research, Division of Systems Biology, Jefferson, AR 72079, USA.; U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD 20993, USA.; Department of Experimental Pharmacology and Translational Science, Chiesi Farmaceutici S.p.A., 43122 Parma, Italy.; Pharma Research and Early Development, Roche Innovation Center Basel, Pharmaceutical Sciences, F. Hoffmann-La Roche, 4070 Basel, Switzerland.; Bristol Myers Squibb, Nonclinical Research and Development, Summit, NJ 07901, USA.; Federal Agency for Medicines and Health Products (FAMHP), Department DG PRE authorization, 1210 Brussels, Belgium.; Eli Lilly, Global Regulatory Affairs, Indianapolis, IN 46285, USA.; Janssen R&D, Preclinical Sciences & Translational Safety, 2340 Beerse, Belgium.; Federal Institute for Drugs and Medical Devices, Clinical Trials, 53175 Bonn, Germany.; Janssen R&D, Drug Metabolism & Pharmacokinetics, 2340 Beerse, Belgium.; GlaxoSmithKline, Non-Clinical Safety, Collegeville, PA 19406, USA.; Janssen R&D, Discovery Sciences, 2340 Beerse, Belgium.; Health and Environmental Sciences Institute, Washington, DC 20005, USA.

DOI: 10.1242/dmm.049065

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MeSH Terms: Bronchopulmonary Dysplasia, Drug Development, Enterocolitis, Necrotizing, Humans, Infant, Newborn, Infant, Newborn, Diseases