Computers at the heart of the matter

Computer scientists at the University of Oxford are developing a way to predict which new drugs could cause heart problems.

New drugs cost pharmaceutical companies millions of pounds to develop, yet almost half of them never make it to market because at a late stage – phase 3  clinical trials – they are discovered to have adverse effects on the human heart, most commonly causing arrhythmia (abnormal beating). Researchers at the University of Oxford are developing computational techniques that have the potential to model the effect of specific pharmacological compounds on the heart and flag up problems much earlier.

David Gavaghan, Professor of Computational Biology, and his colleagues model the electrophysiology of cardiac cells. Electrophysiology – the flow of ions in and out of cells via ion channels – drives the heart by releasing calcium to make the muscles contract and pump blood. Professor Gavaghan’s research group works with pharmaceutical companies including AstraZeneca and GlaxoSmithKline to model the effect that specific drugs have on the cardiac ion channels, either intentionally or otherwise. By modelling the likely effect of a drug on an ion channel, embedding that within a model of a cell and then embedding that within a model of the whole organ, it should become possible to predict which drugs might potentially cause heart problems.

The computer code developed for this application is now open source (i.e. freely available) and has been downloaded by hundreds of groups worldwide. Users include NASA and the US Food and Drug Administration.

Including these computer modelling techniques in the drug development pipeline promises major benefits for the pharmaceutical industry and for patients. By combining these modelling techniques with genetic screening methods to determine which individuals are likely to be susceptible to a particular side effect, it could be possible to accelerate the introduction of new drugs to the market, and potentially to reinstate drugs that are currently withdrawn, for use by individuals in whom they cause no adverse effects.

Funded by: The European Union.