Gene Therapy Rescues Mice With Cardiac Disorder
Brugada syndrome—characterized by an often fatal irregular heartbeat (arrhythmia)—causes sudden cardiac death in relatively young, otherwise healthy individuals between 30 and 40. Paradoxically, most antiarrhythmic agents do not prevent arrhythmias but instead can provoke arrhythmias.
Mutations in SCN5A, encoding cardiac sodium channel NaV1.5, cause 25 to 30% of Brugada syndrome cases. Previously, researchers had found that a small 20-kDa chaperone protein MOG1 binds to NaV1.5 and promotes the trafficking of NaV1.5 to the cell surface.
In this study, researchers from the Cleveland Clinic developed a knock-in mouse model of Brugada syndrome using an SCN5A mutation identified in multiple Brugada syndrome families (Scn5aG1746R/+). Qing K. Wang and colleagues then tested AAV9–MOG1 gene therapy in the mouse model, finding that treatment reversed sodium channel/current defects and corrected cardiac electrophysiological abnormalities and clinical features associated with Brugada syndrome. The researchers supported this strategy by applying it to another heterozygous humanized knock-in mouse model expressing a different SCN5A mutation (p.D1275N). In this model, AAV9-MOG1 increased cell surface NaV1.5 expression, enhanced cardiac sodium current density, and rescued the mild dilated cardiomyopathy (DCM) and cardiac arrhythmia. However, it remains to be determined whether AAV9-MOG1 gene therapy can be extended to more severe forms of DCM and heart failure.
https://www.genengnews.com/news/gene-therapy-rescues-mice-with-cardiac-disorder/
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