Examination of mitochondria- and inflammasome-mediated mechanisms of clozapine-induced myocarditis using patient-derived iPSC cardiomyocytes

Abstract

Clozapine is the only approved pharmacotherapy for treatment-resistant schizophrenia. However, widespread utilization of clozapine is constrained due to the potential for severe adverse effects, including myocarditis. Multiple mechanisms have been suggested to account for the cardiotoxic effects of clozapine, yet these investigations have not used cells derived from clozapine treated patients. In this study, cardiomyocytes that were derived from induced pluripotent stem cells generated from four patients with treatment-resistant schizophrenia with (n = 2) and without (n = 2) a history of clozapine-induced myocarditis were used to assess mitochondria- and NLRP3 inflammasome-mediated mechanism..