Tideglusib在致心律失常性心肌病小鼠模型中的疗效评价

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-08-01 DOI:10.1016/j.jacbts.2025.03.013

Nipun Malhotra MSc , Omer Cavus MD , Michael J. Wallace BS , John T. Bobik BS , Kevin You , Sarah S. Takenaka BS , Danielle Abdallah BS , Eleanor J. Mohler , Steve Antwi-Boasiako BS , Nathaniel P. Murphy MD, PhD , Holly Sucharski-Argall PhD , Xianyao Xu MSc , Stephen P. Chelko PhD , Thomas J. Hund PhD , Jason D. Roberts MD, MAS , Peter J. Mohler PhD , Mona El Refaey PhD

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引用次数: 0

摘要

心律失常性心肌病（ACM）是一种遗传性心脏病，目前的药物治疗是针对电表现的管理。到目前为止，还没有一个解决这种进行性疾病的潜在病理生理。我们评估了Tideglusib （TD）在Ank2心脏选择性敲除和纯合子粘连蛋白2突变型ACM小鼠模型中的治疗效果。TD能够预防和逆转治疗小鼠的心功能下降。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的发生率降低。我们提供了令人信服的TD作为ACM患者潜在治疗方法的临床前数据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy

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.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.