The development of statin-based therapy for patients with hepatitis C virus (HCV) infection using human induced pluripotent stem (iPS) cell technology

Significance Statement

Human induced pluripotent stem cells (hiPSCs) have been expected to transform drug discovery by providing physiologically relevant cells for toxic compound identification and compound screening. When Shimada M et al. (J Hepatol. 2012;56: 299-300) considered two reports (Moriguchi H et al.; Hepatology. 2010; 51: 344–345 and 351–352) published in 2010 investigating the antiviral efficacy of pitavastatin against hepatitis C virus (HCV) infection in vitro, they conducted a randomized controlled trial (J Hepatol. 2012;56: 299-300). As a result, the results of 2010 proof-of-concept studies of the antiviral efficacies and safety of pitavastatin against HCV infection using a replicon system and human hepatocyte-like cells from hiPSCs (Moriguchi H et al.; Hepatology. 2010; 51: 344–345 and 351–352) were confirmed in a randomized controlled trial published by Shimada M et al. in 2012 (J Hepatol. 2012;56: 299-300). Therefore, this series of studies (Moriguchi H et al.; Hepatology. 2010; 51: 344–345 and 351–352, Shimada M et al.; J Hepatol. 2012; 56: 299-300) would be the first to report clinical applications of hiPSCs. Furthermore, after the clinical trial by Shimada M et al. (J Hepatol. 2012; 56: 299-300), the antiviral efficacies and safeties of pitavastatin against HCV infection were more confirmed in the two clinical studies (Kohjima M et al.; J Med Virol. 2013: 85: 250-260 and Yokoyama S et al.; Aliment Pharmacol Ther. 2014; 39: 443-444). Therefore, to investigate the antiviral efficacies and safety of pitavastatin against HCV infection using a replicon system and human hepatocyte-like cells from hiPSCs (Moriguchi H et al.; Hepatology. 2010; 51: 344–345 and 351–352) would be a rational approach as new drug discovery. 

About the author

Dr. Moriguchi H obtained his Ph.D. from the University of Tokyo in 2007. He was a visiting associate professor (full time) from 2000 to 2006 and a project professor from 2006 to 2009 at the University of Tokyo. He is currently at Oak Clinic company. His research focuses on clinical epidemiology (1996, Gut, etc), clinical decision analysis (2002, Hepatology, etc), stem cell research (2011, Cell Mol Life Sci, etc) and reproductive medicine (2012, Hum Reprod, etc) in Gastroenterology, Hepatology, cancers, stem cell research and reproductive medicine.

Journal Reference

Clin Res Hepatol Gastroenterol. 2015;39(5):541-3.

Moriguchi H.

Oak Clinic, 2-7-9, Tamade-Nishi, Nishinari-ku, 557-0045 Osaka, Japan. Electronic address: [email protected].

Abstract

Human induced pluripotent stem (iPS) cells may transform drug discovery. Here I show an example of the development of statin (HMG-CoA reductase inhibitors)-based therapy for patients with hepatitis C virus (HCV) infection using human iPS cell technology. When Shimada et al. considered the two reports on the antiviral effects of pitavastatin for HCV infection in vitro by Moriguchi et al., they conducted a randomized controlled trial. As a result, a proof-of-concept for the antiviral effect of pitavastatin against HCV infection using human iPS cell technology by Moriguchi et al. was confirmed in the randomized controlled trial by Shimada et al. in 2012. Therefore, above-mentioned a series of studies became to the first to report the clinical application of human iPS cells. Furthermore, here I propose that new clinical research methods using human iPS cell technology will be able to circumvent the limitations of conventional randomized controlled trials (RCTs) for the purpose of personalized medicine in the clinical setting.

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