Personalized therapies for cardiac channelopathies

The new target for treatment of patients with long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) is represented by the correction of the arrhythmogenic substrate underlying the disorders, in order to restore a physiological duration of ventricular repolarization in LQTS and a normal intracellular calcium handling in CPVT. This chapter reviews how conventional drugs, such as sodium channel blockers, may be suitable to treat the type 3 LQTS, both reverting the prolongation of QT interval and reducing arrhythmic events caused by abnormalities in the cardiac sodium inward current. Beside conventional drugs, advanced therapy medicinal products have been tested in preclinical studies: these therapies represent nowadays the frontier of medical research and are being tested in thousands of clinical trials in a large variety of indications. The chapter also provides a review of how different gene therapy strategies have been used to rescue the wild-type phenotype in LQTS and CPVT models. Finally, it reports the current limits of gene therapy, reviewing the case of Brugada syndrome that, despite being one of the most prevalent cardiac channelopathies, remains far from the possibility to have a ‘personalized’ therapy.