在致心律失常性心肌病小鼠模型中评估替德格鲁西作为疾病修饰疗法的效果。
Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy.
作者信息
Malhotra Nipun, Cavus Omer, Wallace Michael J, Bobik John T, You Kevin, Takenaka Sarah S, Abdallah Danielle, Mohler Eleanor J, Antwi-Boasiako Steve, Murphy Nathaniel P, Sucharski-Argall Holly, Xu Xianyao, Chelko Stephen P, Hund Thomas J, Roberts Jason D, Mohler Peter J, El Refaey Mona
机构信息
The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart, and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA; Department of Surgery/Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart, and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
出版信息
JACC Basic Transl Sci. 2025 Aug;10(8):101281. doi: 10.1016/j.jacbts.2025.03.013.
Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease, and current pharmacological therapies are directed toward the management of electrical manifestations. To date, none address the underlying pathophysiology of this progressive condition. We evaluated the therapeutic efficacy of Tideglusib (TD) in Ank2 cardio-selective-knockout and homozygous desmoglein-2 mutant ACM mouse models. TD was able to prevent and reverse the reduced cardiac function in treated mice. Moreover, TD-treated adult mice displayed a reduction in ventricular arrhythmia following adrenergic stimulation. We provide compelling preclinical data for TD as a potential therapy for patients with ACM.
致心律失常性心肌病（ACM）是一种遗传性心脏病，目前的药物治疗主要针对电活动表现进行管理。迄今为止，尚无药物能解决这种进行性疾病的潜在病理生理学问题。我们评估了替地格鲁司（TD）在Ank2心脏选择性敲除和纯合桥粒芯糖蛋白-2突变的ACM小鼠模型中的治疗效果。TD能够预防和逆转治疗小鼠心脏功能的降低。此外，经TD治疗的成年小鼠在肾上腺素能刺激后室性心律失常有所减少。我们提供了令人信服的临床前数据，表明TD有可能成为ACM患者的一种治疗方法。
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