Health: Cough medicine helps treat heart conditions in mice and human cells

Studies in mouse models and human cells have shown that the antitussive drug dextromethorphan can help treat potentially life-threatening congenital arrhythmias caused by mutations in three different genes.A paper reporting this finding will be published in Nature Cardiovascular Research.However, further research is needed to investigate the effects on other organs and tissues and to optimize treatments for future clinical applications.

The heartbeat is due to the action of special muscle cells of the heart called cardiomyocytes.This pulsatile process is controlled by the flow of charged ions through the membrane of cardiomyocytes (called action potentials), which excites and contracts the cells.Mutations in the genes that encode ion channels can lead to certain irregular heartbeats (a special arrhythmia called long QT syndrome).One example is Timothy Syndrome, a rare disease with no cure, which leads to death in early childhood.The cause of Timothy syndrome is a mutation in the CACNA1C gene, which is responsible for calcium ion transport.

This time, Masayuki Yazawa and his colleagues at Columbia University have been active when dextromethorphan, an antitussive drug approved by the US Food and Drug Administration, is administered to human cardiomyocytes derived from mice with Timothy syndrome and patients with Timothy syndrome. It was clarified that the potential was normalized.Similar effects were observed in the more commonly seen human cell models of long QT syndrome (LQTS1 and LQTS2). LQTS1 and LQTS2 are caused by mutations in the genes encoding the potassium ion channels KCNQ1 and KCNH2, respectively.Dextromethorphan restores action potentials by suppressing the flow of calcium ions, increasing the flow of potassium ions, and activating the SIGMAR1 receptor.

Yazawa et al. Point out some precautions that may limit the clinical application of dextromethorphan, including the possibility of causing vomiting in some patients.Moreover, the pharmacological properties of dextromethorphan in infants and children (the main patient group with Timothy syndrome) have not been fully elucidated.However, dextromethorphan will be an important stepping stone for the development of treatments for Timothy syndrome.

doi: 10.1038 / s44161-021-00016-2
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* This article is reprinted from "Nature Japan Featured Highlights".
Reprinted from: "Health: Antitussives help improve heart abnormalities in mouse and human cells'

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