We needed to characterise the best available drug in our assays, so that we could demonstrate that our new drug is an improvement, and this paper captures our key findings, giving context to our emerging data.
Dr Michael Curtis, School of Cardiovascular Medicine & Sciences
09 June 2020
Assay validated for characterising a new drug for sudden cardiac death
A team of researchers from the School of Cardiovascular & Medicine Sciences have developed a novel antiarrhythmic drug that appears to be devoid of the adverse effects of those currently available. This research showcases the unique advantage of testing benefit and adversity of a drug simultaneously.
Sudden cardiac death (SCD), due to ventricular fibrillation (VF), is the single largest cause of death in the UK. This means that this type of arrhythmia, is the largest unmet therapeutic target need and remains a substantial clinical burden.
Antiarrhythmic drugs, used to resolve cardiac rhythm disturbances, have failed against SCD when tested in humans due to adverse effects or have failed to provide benefits due to the low doses that need to be administered. Of the two drugs currently used, amiodarone and mexiletine, mexiletine remains the global standard of its class.
The researchers, consisting mostly of MSc and BSc project students, led by Dr Michael Curtis, who has over 30 years’ experience conducting research in this area, have developed a novel class 1b drug that appears to be devoid of the adverse effects previously seen.
The new drug is ischaemia-activated pro-drug and works when there is an inadequate blood supply in part of the heart. The team has used a rat isolated heart SCD bioassay as their main model for testing the drug and it appears to be exclusively ischaemia-selective.
To illustrate that the new drug is much safer than mexiletine at concentrations suppressing VF, the team published a template data set for mexiletine in the rat isolated heart SCD bioassay. The study found that mexiletine has good effects on VF but has adverse effects at the same dose, meaning that it has no meaningful therapeutic window in this assay, also known as its ‘translational therapeutic index’.
The study showed that the team’s approach of testing benefit and adversity in the same experiment provides a reliable translational therapeutic index, unlike mexiletine.
The full study can be found published in Scientific Reports and sets the standard that must be beaten by any new drug.
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