Why the study?
Clozapine has superior efficacy in refractory schizophrenia, but its clinical use is limited by severe adverse effects including myocarditis.
The generation of patient-specific iPSC lines provides a novel cellular model to investigate the mechanisms underlying clozapine-induced myocarditis.
Patient-specific iPSCs enable modeling of clozapine myocarditis; leaves open predictive biomarker discovery before clinical use.
Clozapine has superior efficacy in the treatment of refractory schizophrenia; however, use of clozapine is limited due to severe side effects, including myocarditis. Using non-integrative Sendai virus, we generated induced pluripotent stem cell lines from peripheral blood mononuclear cells of two patients with refractory schizophrenia, one clozapine-tolerant and one clozapine-induced myocarditis. Both cell lines exhibited a normal karyotype and pluripotency was validated by flow cytometry, immunofluorescence and their ability to differentiate into the three germ layers. These lines can be used to generate 2D and 3D patient-specific human cellular models to identify the mechanism by which clozapine induces myocardial inflammation.
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Vaziri et al. (2022) studied this question.
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