Establishment of a new therapeutic protocol for cardiomyopathy in Duchenne muscular dystrophy.

杜氏肌营养不良症（DMD）经常引起心肌病。由于家庭呼吸机和氧疗的发展，呼吸衰竭的死亡率已显著降低，病人的寿命比以前更长。相反，心力衰竭的死亡率正在上升。为了揭示DMD患者发生心肌病的机制，我们从DMD患者中产生iPSC，并从iPS细胞分化心肌细胞。当我们测量细胞内游离钙离子浓度时，在源自DMD-iPS心肌细胞的心肌细胞中钙水平显著升高。此外，在牵张后，DMD-iPSCs诱导的心肌细胞比对照组hiPSCs诱导的心肌细胞更明显地出现钙超载，提示钙超载是DMD患者心肌病的发病机制之一。降低钙超载将是DMD心肌病患者的治疗方法之一。

Duchenne muscular dystrophy (DMD) frequently causes cardiomyopathy. Because of development of home respirator and oxygen treatment, a death rate by respiratory failure has been remarkably reduced and the patients live longer than before. In contrast, the death rate by heart failure is increasing. To reveal mechanisms of developing cardiomyopathy in DMD patients, we generated iPSC from a DMD patient and differentiated cardiomyocytes from the iPS cells. When we measured intracellular free calcium ion concentration, calcium level was remarkably elevated in the cardiomyocytes derived from DMD-iPS cardiomyocytes. Moreover, calcium overload was observed much more clearly in cardiomyocytes derived from DMD-iPSCs than in cardiomyocytes derived from control-hiPSCs after compulsory stretching.These findings indicated that calcium overload is one of the mechanisms for cardiomyopathy in DMD patients. Reducing calcium overload will be one of the treatments for DMD cardiomyopathy patients.