Preclinical testing typically includes testing in animals to determine whether a drug candidate is toxic. Animal studies has its own limitations such as ethical concerns and also some studies point out that animal studies can predict toxicity correctly in only 70% of cases, which makes researchers lose valuable time and resources investigating the wrong drugs. Stem cells are emerging as an alternative to animal testing in recent years. The biggest impact to date of induced pluripotent stem cell technology is not regenerative medicine, but in making disease models, drug discovery, and toxicology studies.
A recent study on 640 novel therapeutic drugs found that more than half (54%) failed in clinical development, most (57%) due to insufficient efficacy, and a sizable proportion (17%) due to safety concerns. If these risks are accurately assessed in the earlier stage of the development process, then it will have less impact on human health and the financial risk associated with taking a compound forward into clinical testing. The use of stem cell-derived human cell lines in preclinical toxicity testing holds a lot of promise of detecting potentially harmful on- and off-target effects of drug candidates before these compounds progress to clinical trials that will help in reduce attrition rates, costly program failures and post-market withdrawals. If adverse effects are detected early, there may be time for cost-efficient modification of the drug to minimize its toxicity.
Cardiotoxicity is one of the top three causes of post-marketing drug withdrawals due to adverse reactions and in recent years rapid advances are being made in the use of hiPSC-derived cardiomyocytes to test drug candidates for their potential to cause electrophysiological or structural changes that can adversely affect myocardial contractility. In a comprehensive review article on using hiPSC-derived cardiomyocytes to assess drug-induced structural cardiotoxicity, authors from the FDA emphasize the renewable and readily scalable nature of stem cells and the benefits of testing directly in human cardiomyocytes rather than having to translate findings from toxicity studies conducted in animal models or animal cell lines.
- A team at GE Healthcare has pioneered a stem cell model to avoid using live creatures. The researchers of the company also are developing drug discovery assays that use human cells to predict toxicity. Biotech giant Genentech is already using stem cell-derived cardiomyocytes from GE Healthcare and Cellular Dynamics International to build a toxicity model to replace animal testing.
– Arpitha Shetty,