Computational prediction of drug cardiac toxicity
Such simulations will involve modelling of drug interactions at the molecular and cellular level, will extend current technology to enable prediction of the effects of those interactions on the dynamics of the whole heart, and will lead to an understanding of how genetic factors can be used to assess patient-specific risk profiles. This requires a multi-level systems approach, based on multi-scale, multi-physics methods, including computations on adaptive spatial grids and multi-grid time integration. Computations on realistic models at appropriate spatial and temporal scales are currently not feasible, so we will investigate new algorithms and their implementation on high-performance platforms, including a new generation of petaflop computers, to achieve 'faster than real-time' simulation.
These tools form part of the infrastructure required to simulate the physiology of major organ systems, thereby contributing to the goal of creating the Virtual Physiological Human (VPH). The balanced team in this project, including founders of the Human Physiome Project, has decades of experience in the experimental study and modelling of the electrophysiology and mechanics of the heart, while pharmaceutical industry partners bring deep understanding of the mechanisms of drug actions. The results will demonstrate the value of the VPH initiative to fundamental scientific understanding of the heart, with major economic and clinical impacts through accelerated drug development, approval and use.
Computational assessment of drug−induced effects on the electrocardiogram: from ion channel block to body surface potentials
N Zemzemi‚ MO Bernabeu‚ J Saiz‚ J Cooper‚ P Pathmanathan‚ GR Mirams‚ J Pitt−Francis and B Rodriguez
In British Journal of Pharmacology. Vol. 168. No. 3. Pages 718−733. 2013.
Simulation of multiple ion channel block provides improved early prediction of compounds' clinical torsadogenic risk
G. R. Mirams‚ Y. Cui‚ A. Sher‚ M. Fink‚ J. Cooper‚ B. M. Heath‚ N. C. McMahon‚ D. J. Gavaghan and D. Noble
In Cardiovascular Research. Vol. 91. No. 1. Pages 53–61. 2011.