Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery

Author:

Ewart Lorna1,Dehne Eva-Maria2,Fabre Kristin3,Gibbs Susan45,Hickman James6,Hornberg Ellinor7,Ingelman-Sundberg Magnus8,Jang Kyung-Jin9,Jones David R.10,Lauschke Volker M.8,Marx Uwe2,Mettetal Jerome T.3,Pointon Amy1,Williams Dominic1,Zimmermann Wolfram-Hubertus1112,Newham Peter1

Affiliation:

1. Drug Safety and Metabolism, Innovative Medicines and Early Development, AstraZeneca, Cambridge CB4 0WG, United Kingdom;

2. TissUse, Berlin 13347, Germany

3. Drug Safety and Metabolism, Innovative Medicines and Early Development, AstraZeneca, Waltham, Massachusetts 02451, USA

4. Department of Dermatology, VU University Medical Center, 1081 HZ Amsterdam, The Netherlands

5. Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University, 1081 LA Amsterdam, The Netherlands

6. NanoScience Technology Center, University of Central Florida, Orlando, Florida 32826, USA

7. Drug Safety and Metabolism, Innovative Medicines and Early Development, AstraZeneca, 431 83 Mölndal, Sweden

8. Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, 171 77 Stockholm, Sweden

9. Emulate Inc., Boston, Massachusetts 02210, USA

10. Medicines & Healthcare Products Regulatory Agency, London SW1W 9SZ, United Kingdom

11. Institute of Pharmacology and Toxicology, University Medical Center Goettingen, Goettingen 37075, Germany

12. German Center for Cardiovascular Research (DZHK), Goettingen 37075, Germany

Abstract

Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug safety and metabolism. By focusing on MPS models that have been developed for these organs, alongside other relevant in vitro models, we review the current state of the art and the challenges that still need to be overcome to ensure application of this technology in enhancing drug discovery.

Publisher

Annual Reviews

Subject

Pharmacology,Toxicology

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