More reliable drug safety testing

The preDiCT project (2008-2011) worked to model, simulate, and predict the impact of drugs on the heart's rhythm using computer models.

About 50% of promising drug candidates are abandoned because of potential cardiac side effects. One of the most dangerous cardiac side effects, Torsades-de-Pointes (TdP), is linked to inhibition of an ion channel called hERG. Current best practice in pharmaceutical development relies on early-stage screening, automatically rejecting compounds that act strongly on the hERG channel. However, there are many drugs which cause TdP but are not hERG inhibitors, and drugs that are hERG inhibitors, but do not lead to arrhythmia.

preDiCT modelled drug interactions at the subcellular (ion-channel) level, and incorporated these processes into cellular and tissue models, to predict drug effects on whole-heart behaviour. The project created a new state-of-the-art for speed, reliability, level of detail and usability of all these models. Furthermore, the project developed a methodology for predicting dangerous drug effects with much greater accuracy than the current best-practice safety test. The improved sensitivity of this methodology was the result of considering the interaction of multiple ionic currents, rather than focusing on a drug’s action on a single ion channel (as in current best-practice for drug safety screening). read more