The cough medicine dextromethorphan has been shown to help treat potentially fatal congenital heartbeat irregularities caused by mutations in three different genes in mouse models and human cells, according to a paper in Nature Cardiovascular Research. However, further research will be needed to investigate the effects on different organs and tissues, and to optimize therapies for future clinical applications.
Specialized heart muscle cells known as cardiomyocytes allow the heart to beat. This process is controlled by the conduction of electrically charged ions across their cell membranes (referred to as the action potential), which in turn become excited and contract. Mutations in genes that encode ion channels can lead to a specific form of arrhythmia or irregular heartbeat known as long QT syndrome. One example is Timothy syndrome, a rare and untreatable disease that leads to early childhood death. Timothy syndrome is caused by mutations in the CACNA1C gene that is responsible for transporting calcium ions.
Masayuki Yazawa and colleagues demonstrate that treating mice born with Timothy syndrome and human cardiomyocytes derived from patients with Timothy syndrome with a US Food and Drug Administration-approved cough suppressant — dextromethorphan — can lead to normalization of the action potential. A similar effect was also observed in human cellular models of more common forms of long QT syndrome — LQTS1 and LQTS2 — that are caused by mutations in the genes that encode potassium ion channels, KCNQ1 and KCNH2, respectively. Dextromethorphan restored the action potential by reducing the flow of calcium ions and increasing the flow of potassium ions, activating the SIGMAR1 receptor.
The authors point out several caveats that could limit the clinical application of dextromethorphan, such as the potential to induce nausea in some patients. In addition, the pharmacological profile of dextromethorphan in infants and young children — the main demographic of patients with Timothy syndrome — is not yet fully understood. Dextromethorphan could, however, represent an important stepping stone towards creating a therapy for these diseases.
Criminology: Predicting police enforcement bias in major US citiesNature Human Behaviour
COVID-19: Assessing instances of long COVID in UK health dataNature Communications