Making new medicines safer
Software developed by mathematical biologist Gary Mirams is revolutionising drug testing across the world by identifying risks to patients earlier and faster.
Before pharmaceutical drugs are made available to patients, they undergo rigorous processes to ensure they are safe, which involve extensive lab-based testing ahead of clinical trials. It is a time consuming and expensive business to get a drug to market with the process from lab to patient taking up to 12 years and costing hundreds of millions of dollars.
Meanwhile patients are waiting for new ways to treat illness and disease.
Professor Gary Mirams has developed a way to improve the process making it easier to identify at an early stage if a drug is likely to have a side effect on the heart, which reduces the use of animals in drug testing, saves the pharmaceutical industry time and money, and reduces the risk to those enrolled in clinical trials and ultimately patients.
Some pharmaceutical drugs can cause potentially fatal changes to the heart’s rhythm, due to binding to particular ion channel proteins and blocking the ionic currents that flow through them. As an example, in the 1990s a hayfever drug was taken off the shelves following a safety warning after being linked to cases of sudden cardiac death.
Professor Mirams and his team have developed mathematical models of ion currents and computer simulations of how they combine to control the heart’s electrical activity, and use them to predict whether a drug will interfere with the heart’s normal electrical rhythm.
"I find it incredibly rewarding applying mathematics to real world problems. Knowing that this technology could have a global impact is phenomenally exciting."
Following collaboration the tool has been embedded within pharmaceutical giants GlaxoSmithKline and Hoffman-LaRoche, while the simulation software is also accessible through a public portal where it has been used by researchers from over 125 other organisations including global pharmaceutical companies and regulators who input their own safety test data to get a prediction of overall changes to heart rhythm. This has made a significant reduction in the number of animal-based heart safety experiments undertaken in industry.
This work has the potential to be used globally as international guidelines are being re-examined to include this simulation approach as standard for all new drug compounds. Professor Mirams is helping regulators including the US Food and Drug Administration with the Comprehensive in-vitro Proarrhythmia Assay initiative (CiPA), which is using mathematical models to improve risk assessment for new drugs in the pharmaceutical industry and exploring how to improve them in the future. The vital impact of this work is underpinned by a £1.9m Wellcome Senior Research Fellowship that was awarded to Professor Mirams in 2019.
He said: “I find it incredibly rewarding applying mathematics to real world problems. If we can filter out compounds that will cause side effects on people’s hearts at an early stage, then pharmaceutical companies will be able to concentrate their efforts on compounds that won’t. It will ultimately mean patients get new treatments sooner that are safer.”
Professor Mirams said: “It’s amazing when you see mathematical models accurately predicting some behaviour that they’ve never seen before, it gives you confidence the biological and physical assumptions that we built into the models are correct, and that they will be able to make reliable predictions in the future. Knowing that this technology could have a global impact is phenomenally exciting.”