An over-the-counter cough suppressant can knock some heart cells out of arrhythmia, a discovery that could lead to a new treatment for long QT syndrome. The finding, which was published in Nature Cardiovascular Research, was made using stem cells from patients with the disorder.
The QT interval on an electrocardiogram (ECG) represents the duration of the ventricular action potential, and this physiologically correlates with the duration of the ventricular depolarisation and repolarisation. Cardiac events and fatal arrhythmias may occur when the QT interval is prolonged either congenitally or through acquired causes. In people with long QT syndrome, cardiac cells are not always ready to produce the next beat, a situation that can knock the heart out of its normal rhythm, which may be life-threatening. For many people with long QT, no treatment can correct the heart cells or prevent arrhythmia.
Using mice to investigate how human heart arrhythmias can be stopped is difficult, so Masayuki Yazawa, PhD at the University of Columbia, turned to patient-derived reprogrammed stem cells, which can be made into heart cells in the lab.
The road to the discovery began several years ago when Dr Yazawa found that heart cells in the lab would resume a normal rhythm when a certain enzyme was inhibited. But the drugs used to inhibit the enzyme also had other unintended effects, such as liver toxicity, so alternatives were needed.
Looking through published research, the team learned that the enzyme could be inhibited through an intermediary molecule inside heart cells called SIGMAR1. Further reading suggested that SIGMAR1 could be targeted by a cough suppressant, dextromethorphan.
Dr Yazawa’s team found that the cough suppressant, when added to heart cells, successfully prepared the heart cells for the next beat and soothed the cells’ irregular rhythm.
The cough suppressant reset heart cells from people with Timothy syndrome, a genetic disorder that also causes other heart abnormalities, and from people with more common forms of long QT syndrome.
Dr Yazawa cautioned that it’s premature to use dextromethorphan to treat long QT patients; the drug has a short half-life and would have to be used long term, which might still have unknown adverse side effects.
“But our study shows that drugs targeting SIGMAR1 have potential to treat a wide array of patients with long QT syndrome,” said Dr Yazawa, “and we will continue to look for better options.”
Source: Columbia University
