Toxicity modelling in drug discovery

A surprisingly common reason for development of a new drug to be discontinued, or for drugs to be withdrawn from sale once on the market, is a risk of potentially-fatal side effects on the heart. This has even been a problem for non-heart drugs such as hayfever tablets. We aim to predict whether any new drug will have such effects by using mathematical models for the electrical activity of the heart. We study how the heart’s electrical activity is affected by drug compounds binding to the proteins that carry electrical charge in and out of heart cells, and whether resulting changes to heart rhythm will be dangerous or not.

We have introduced these simulations into drug development within pharmaceutical companies, to make more accurate predictions of risk for new drug molecules, earlier in drug development, and thereby to reduce the use of animal testing. Working closely with the Food & Drug Administration in the USA we are contributing to the Comprehensive in-vitro Pro-arrhythmia Assay (CiPA) which proposes that now is the time to introduce mathematical models into a core role in regulatory testing for drug safety in the heart.