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Application of Wnt inhibitor Wnt-C59 in preparation of medicine for treating dilated cardiomyopathy caused by SCN5A mutation

A technique for dilated cardiomyopathy and wnt-c59, which is applied in the field of biomedicine to achieve good application prospects and improve the prognosis of cardiac function

Active Publication Date: 2021-03-12
ZHONGSHAN HOSPITAL FUDAN UNIV
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Problems solved by technology

There is no report about the application of the Wnt inhibitor Wnt-C59 of the present invention in the preparation of drugs for the treatment of dilated cardiomyopathy caused by SCN5A mutations

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  • Application of Wnt inhibitor Wnt-C59 in preparation of medicine for treating dilated cardiomyopathy caused by SCN5A mutation
  • Application of Wnt inhibitor Wnt-C59 in preparation of medicine for treating dilated cardiomyopathy caused by SCN5A mutation
  • Application of Wnt inhibitor Wnt-C59 in preparation of medicine for treating dilated cardiomyopathy caused by SCN5A mutation

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Embodiment 1

[0025] Embodiment 1 Animal experiment

[0026] 1 method

[0027] 1.1 Preparation of experimental animals and animal models

[0028] SPF grade male C57BL / 6 mice (purchased from Shanghai Jiesijie Experimental Animal Co., Ltd.) and SCN5A heterozygous mutant mice were selected, aged 8-10 weeks, weighing 20-25g, and treated with d-galactose (500mg / kg.d, sigma G5388) were injected intraperitoneally for 8 weeks to construct an aging model. Then, doxorubicin (10 mg / kg in total, injected intraperitoneally in 4 times, Sanko A603456) was used to construct a heart expansion model. After the model was established, the cardiomyocytes of mice in the KI group and the WT group were isolated. The experimental protocol was approved by the Animal Management and Ethics Committee of Fudan University.

[0029] Animal experiments have shown that there is no statistical difference in heart function between SCN5A heterozygous mutant mice and wild-type mice in the natural aging model, the simple ga...

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Abstract

The invention relates to the technical field of biological medicines, in particular to application of a Wnt inhibitor Wnt-C59 in preparation of a medicine for treating dilated cardiomyopathy caused bySCN5A mutation. According to the invention, SCN5A genotype detection is used as an entry point for the first time, and a Wnt pathway specific inhibitor Wnt-C59 is used for inhibiting abnormal activation of a Wnt / beta-Catenin pathway caused by SCN5A gene mutation, so that the prognosis of the cardiac function of an expanded cardiomyopathy patient with SCN5A gene mutation is improved. According tothe experiment, the treatment effect of Wnt-C59 on the dilated heart disease is detected by constructing an aging and adriamycin induced dilated heart disease model, changing the cardiac function, activating related signal molecules and other indexes, and a theoretical basis is provided for application of Wnt-C59 to clinical treatment of dilated cardiomyopathy. The invention provides a new treatment method for the dilated cardiomyopathy caused by SCN5A mutation, brings dawn to the patients, and has a good application prospect.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of Wnt inhibitor Wnt-C59 in the preparation of drugs for treating dilated cardiomyopathy caused by SCN5A mutation. Background technique [0002] Primary dilated cardiomyopathy (dilated heart disease) refers to the irreversible decline in heart function caused by heart enlargement. The prevalence of the population is about 40 / 100,000, and the 5-year mortality rate reaches 50%. There is no specific treatment plan. Cardiac expansion caused by genetic factors accounts for about 20-30%. It was initially found that the pathogenic genes mostly encode cell structural proteins, such as cardiac actin (actin) gene, nuclear lamin (laminA / C) gene, etc., due to damage Cellular stress transmission leads to myocardial damage and heart enlargement. In 2004, McNair proposed for the first time that the mutation of the cardiac sodium channel gene (SCN5A) was related to heart exp...

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Application Information

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IPC IPC(8): A61K31/444A61P9/04
CPCA61K31/444A61P9/04Y02A50/30
Inventor 葛均波孙爱军胡静静杨坤
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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