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Enzyme replacement therapy (ERT), with recombinant \u03b1\u2010galactosidase A, is currently available for use to reduce GL\u20103 deposits. However, although it improves cardiac function and decreases left ventricular mass, GL\u20103 clearance upon ERT has been demonstrated in cardiac capillary endothelium but not in cardiomyocytes of patients. Relevant models are needed to understand the pathogenesis of cardiac disease and explore new therapeutic approaches. We generated induced pluripotent stem cells (iPSC) from Fabry patients and differentiated them into cardiomyocytes. In these cells, GL\u20103 accumulates in the lysosomes over time, resulting in phenotypic changes similar to those found in cardiac tissue from Fabry patients. Using this human in vitro model, we demonstrated that substrate reduction therapy via glucosylceramide synthase inhibition was able to prevent accumulation and to clear lysosomal GL\u20103 in cardiomyocytes. This new in vitro model recapitulates essential features of cardiomyocytes from patients with Fabry disease and therefore provides a useful and relevant tool for further investigations of new therapy.<\/jats:p>","DOI":"10.1007\/s10545-014-9724-5","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T11:38:48Z","timestamp":1400672328000},"page":"1013-1022","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Effective clearance of GL\u20103 in a human iPSC\u2010derived cardiomyocyte model of Fabry disease"],"prefix":"10.1002","volume":"37","author":[{"given":"Jean\u2010Michel","family":"Itier","sequence":"first","affiliation":[{"name":"Bio\u2010Innovation, Global Biotherapeutics, SANOFI 13 quai Jules Guesdes Vitry\u2010sur Seine 94400 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