Project: Early and predictive cardiac safety assessment of drugs using an automated system with human cardiac cells.

BACKGROUND_x000D__x000D_Pharmaceutical drug discovery and development is an expensive, high-risk business characterized by long time lines (8-12 years from early discovery work to market authorization, figure 1 in Appendix). The decision-making process to select promising potential drugs as pre-clinical candidates relies heavily on specific and predictive assays to distinguish beneficial on-target effects from detrimental side effects. The cardiovascular system is of particular interest for any kind of potential drug since effects on the heart may be immediately life threatening._x000D__x000D_THE PROBLEM_x000D__x000D_However, one of the most difficult tasks in cardiac safety pharmacology is how best to conduct reliable screening to predict the effect of experimental drugs on the cardiac system at an early stage in drug discovery & development. Since current (essentially animal based) model systems have their limitations (Meyer et al., 2007), there is an urgent unmet need for reliable cardiac assays which recapitulate the complex ion-channel interactions of cardiomyocytes in the human heart, to identify potential compound risks early in drug development, allowing reduction in animal use, time and cost to market._x000D__x000D_OUR SOLUTION_x000D__x000D_Human pluripotent stem cells are a renewable and reproducible source of cardiomyocytes (hPSC-CM) that share many features of human adult ventricular cardiomyocytes (Braam et al., 2010). The potential of disease models based on human pluripotent stem cell derived cardiomyocytes has been convincingly proven in a number of scientific publications (Braam et al., 2010; Itzhaki et al., 2011; Liang et al., 2010). These cells, in combination with multi-well micro-electrode arrays and advanced data analysis software solutions, will make an attractive powerful system to predict the effect of potential drugs on cardiac electrical activity (figure 2 in Appendix)._x000D__x000D_To allow broad scale application of such a system, a well-validated reproducible cardiomyocytes cell source should be combined with dedicated hardware and software. In the current project we will combine the cell-biological experience of the Dutch start-up Pluriomics with the microelectrode array expertise of the German SME Multi Channel Systems and the software capabilities of the French SME NOTOCORD Systems. The combination of these technology platforms will allow us to make crucial steps towards the validation of a predictive model for drug screening based on human stem cell._x000D__x000D_The final goal is to market an industry standard hPSC-CM based solution for cardiac safety pharmacology. In particular the system could be used to bridge the gap between current high-througput compound risk identification assays (COly hERG) and the expensive and time consuming pre-clinical validation studies. In addition the system could be used early in compound development to identify possible cardiac side effects, for assessing structure activity relationships with the cardiac side effects, and possibly for full risk-assessment.

Acronym CardioXpress (Reference Number: 7576)
Duration 01/11/2012 - 30/10/2014
Project Topic The expected result of the project is a fully integrated, automated cardiac safety pharmacology platform which combines human cardiomycoytes derived from stem cells, with a multi-well electrophysiological recording hardware ,and powerfull software for data collection, analysis and reporting.
Project Results
(after finalisation)
A desktop application software to analyze with high confidence the large volume of signals from Multi Channel Systems devices generated files.
Network Eurostars
Call Eurostars Cut-Off 8

Project partner

Number Name Role Country
3 Pluriomics BV Partner Netherlands
3 NOTOCORD SYSTEMS SAS Coordinator France
3 Multi Channel Systems MCS GmbH Partner Germany