抄録
The goal of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative is to evaluate proarrhythmic risk based on a mechanistic electrophysiological understanding of proarrhythmia that has improved specificity compared with the current paradigm using the hERG assay plus the Thorough QT study. The three primary components of CiPA include, in vitro drug effects on multiple cardiac ion channels, in silico reconstruction of electrical effects and integrated evaluation using human stem-cell derived cardiomyocytes (hSC-CM).
The role of hSC-CM assay is to confirm the cellular electrophysiological effects to be derived from the in silico reconstructions based on effects on individual ionic currents, and to inform knowledge of repolarization effects not anticipated from ion channel or in silico reconstruction efforts. To achieve this objective, it must first be demonstrated that hSC-CM’s and technological platform/approaches provide reasonable throughput and reproducibility of results between and across laboratories. A multi-disciplinary approach is required to assess both the cells and technologies being developed, and to acquire data needed for CiPA and translational science decision-making. Under the auspices of the HESI Cardiac Safety Committee, the Myocyte Subteam was formed, designed and completed a pilot study to assess multi-electrode array and voltage sensitive optical platforms (to assess electrophysiologic effects based on field potential measures and transmembrane potentials, respectively). This talk with cover updates from the CiPA initiative and detail the work of the Myocyte Subteam in the context of the evolving CiPA paradigm.
