How effective are nonalcoholic fatty liver disease models for drug discovery?

Expert Opinion on Drug Discovery
Jana Hundertmark, Frank Tacke

Abstract

The spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) with hepatic fibrosis up to liver cirrhosis and hepatocellular carcinoma, displaying a global health problem with no effective therapy yet. Multiple preclinical models reflecting different aspects of the disease helped to identify a variety of different targets over the last years. However, some recent clinical trials have revealed a lack of translatability, emphasizing the need for more effective preclinical research. In this editorial, we discuss different NAFLD mouse models as well as emerging ex vivo and in vitro models that have been used in drug discovery and dissect the translational challenges that have to be considered in drug development.

References

Oct 11, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Geoffrey C FarrellClaire Z Larter
Jan 28, 2017·World Journal of Gastroenterology : WJG·Tomasz KostrzewskiDavid J Hughes
Jan 31, 2017·Gastroenterology·Cristina AlonsoJosé M Mato
Nov 13, 2017·Journal of Hepatology·Prasanna K SanthekadurArun J Sanyal
Jun 4, 2019·Cell Metabolism·Rie OuchiTakanori Takebe
Jul 14, 2019·Journal of Hepatology·Mary E RinellaUNKNOWN participants of the AASLD/EASL Workshop
Jan 8, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shabir HassanAli Zarrinpar
Feb 12, 2020·Gastroenterology·Mohammed EslamUNKNOWN International Consensus Panel
Mar 10, 2020·Journal of Hepatology·Stephen A HarrisonUNKNOWN STELLAR-3 and STELLAR-4 Investigators

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Citations

Dec 31, 2020·Journal of Clinical Medicine·Pierre-Antoine SoretJérémie Gautheron
Apr 20, 2021·Basic & Clinical Pharmacology & Toxicology·Magnus Ingelman-Sundberg, Volker M Lauschke
Sep 18, 2021·ACS Medicinal Chemistry Letters·Joseph CarpenterDean A Wacker

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