A role for in vitro disease models in the landscape of preclinical cardiotoxicity and safety testing

Vijayalakshmi Varma,Cheng Wang

doi:10.14302/issn.2574-4372.jesr-17-1705

Vijayalakshmi Varma, Cheng Wang

Open Access

https://doi.org/10.14302/issn.2574-4372.jesr-17-1705

Copy DOI

Abstract

A role for in vitro disease models in the landscape of preclinical cardiotoxicity and safety testing

Highlights

JOURNAL OF EVOLVING STEM CELL RESEARCHA Role for In Vitro Disease Models in The Landscape of Preclinical Cardiotoxicity and Safety Testing
The drug development pipeline is an arduous, labor-intensive and expensive process that entails stringent regulations by the Food and Drug Administration (FDA), in order to ensure the final marketed drug will be safe and efficacious for use in all patients that are prescribed the drugs [1,2,3]
A potential reason for late-stage drug attrition and post-marketing withdrawals may be attributed to drug-induce cardiotoxicity augmented by cardiovascular risk factors that are prevalent in many patients with metabolic disorders such as obesity (36% of the population [9] type II diabetes (9.3% of the population [10], and metabolic syndrome (~35% of the population) [11]

Summary

JOURNAL OF EVOLVING STEM CELL RESEARCH

A Role for In Vitro Disease Models in The Landscape of Preclinical Cardiotoxicity and Safety Testing. Abstract : Drug-induced cardiotoxicity is one of the predominant reasons for drug attrition and withdrawals. This is of critical concern when potentially cardiotoxic drugs are administered to individuals with inherited arrhythmogenic cardiac diseases or with metabolic diseases such as obesity and diabetes, which are key risk factors for cardiovascular diseases. Screening for drug-induced cardiotoxicity early in the preclinical stages of drug development, by using appropriate human disease models, can be effective in ensuring safety in clinical trials and preventing late stage and post-marketing drug withdrawals owing to cardiotoxicity. The ability to generate patient-specific iPSCs that can model cardiac diseases, offers a valuable option that can further improve drug safety assessments and enable a more accurate prediction of toxicity that occurs in the representative population that are prescribed the drugs. Received: July 13, 2017 Accepted: July 21, 2017 Published: July 29, 2017 www.openaccesspub.org | JESR

Introduction

Limitations of current models and strategies

Cardiovascular disease models and its applications

Conclusions