时间：2016-12-03 16:18:03 阅读：866
|Title:||Moving from hERG to CiPA ------ Evolution of preclinical cardiac assessment and ICE’s practices|
The assessment of drug-induced hERG(human Ether-à-go-go-Related Gene) block has become a standard component in cardiac safety evaluations during nonclinical drug development. However, hERG block alone may not be accurate in predicting the risk of QT prolongation.The ECG and cardiac action potential are formed by many different ion channels. hERG block does not always prolong QT due to mixed ion channel effects, including Nav1.5, Cav1.2, Kv1.5, etc. The best description for cardiac safety is to understand mechanisms of action potential which could be achieved by thorough safety package assessment. Here, we introduce a more comprehensive assay to evaluate the cardiac safety of drugs: the Comprehensive in Vitro Proarrhythmia Assay (CiPA).The evaluation of drug effectswith multi ion channel effects (MICE), has been proved to be superior to the HERG model in predicting drug-induced proarrhythmia, or more specific, Torsades de Points (TdP), Moreover, as a part of CiPA, we offer the stem cell-derived human cardiomyocytesas a nonclinical safety assay in predicting the cardiac risksof drugs.The “off the shelf” availability of cardiomyocytes in large quantities is very appealing due to the potentials to overcome shortcomings of recombinant cell lines, which may not recapitulate physiological conditions, native human tissues which are expensive, andnon-human models which may not reflect human physiology.
Weimin Pei, Ph.D, is now the Chief Scientific Officer (CSO) of ICE bioscience Inc., in Beijing, China. Dr. Pei had been working in Chantest, the No. 1 ion channel testing service company in the world, for 10 years, and was taking charge of the patch clamp team as research director/senior scientist from 2014 to 2016. Dr. Pei has collaborated with almost all world-famous pharmaceutical companies on physiological and pharmacological mechanisms of ion channels, safety assessment, drug discovery, and cell line validation.Dr. Pei is richly experienced in over 100 ion channels, both commercially and academically. Dr. Pei received his Ph.D degree from State University of New York at Albany in 2006, majored inNeuroscience & Chemistry.Most of his works during his Ph.D and post-doctoral training in the State University of New York at Albanywere published as high quality papers in prestigious peer-reviewed journals, such as Nucleic Acids Research and Biochemistry.