Title:
USE OF WNT INHIBITOR WNT-C59 IN PREPARATION OF DRUG FOR TREATING DILATED CARDIOMYOPATHY CAUSED BY SCN5A MUTATION
Document Type and Number:
WIPO Patent Application WO/2022/116583
Kind Code:
A1
Abstract:
Disclosed in the present invention is the use of a Wnt inhibitor Wnt-C59 in the preparation of a drug for treating dilated cardiomyopathy caused by SCN5A mutation. Proposed for the first time in the present invention is that SCN5A genotype detection is used as an entry point, and a Wnt pathway specific inhibitor Wnt-C59 is used for inhibiting the abnormal activation of a Wnt/β-Catenin pathway caused by a SCN5A gene mutation, so that the prognosis of the cardiac function of a patient with dilated cardiomyopathy due to the SCN5A gene mutation is improved. According to the experiment, the treatment effect of Wnt-C59 on dilated cardiomyopathy is detected by means of constructing a dilated cardiomyopathy model induced by aging in combination with adriamycin and using indicators such as changes in cardiac function and the activation of related signal molecules, which provides a theoretical basis for the clinical use of Wnt-C59 in the treatment of dilated cardiomyopathy. The present invention provides a new method for treating dilated cardiomyopathy caused by SCN5A mutation.
Inventors:
GE JUNBO (CN)
SUN AIJUN (CN)
HU JINGJING (CN)
YANG KUN (CN)
SUN AIJUN (CN)
HU JINGJING (CN)
YANG KUN (CN)
Application Number:
PCT/CN2021/111105
Publication Date:
June 09, 2022
Filing Date:
August 06, 2021
Export Citation:
Assignee:
ZHONGSHAN HOSPITAL FUDAN UNIV (CN)
International Classes:
A61P9/04; A61K31/444
Foreign References:
| CN112472701A | 2021-03-12 | |||
| CN102369187A | 2012-03-07 | |||
| US10624949B1 | 2020-04-21 |
Other References:
LU AIZHU, KAMKAR MARYAM, CHU CENCEN, WANG JERRY, GAUDET KAYA, CHEN YAWEN, LIN LAUREN, LIU WEIXIN, MARBÁN EDUARDO, LIANG WENBIN: "Direct and Indirect Suppression of Scn5a Gene Expression Mediates Cardiac Na+ Channel Inhibition by Wnt Signalling", CANADIAN JOURNAL OF CARDIOLOGY, vol. 36, no. 4, 1 April 2020 (2020-04-01), CANADA , pages 564 - 576, XP055935723, ISSN: 0828-282X, DOI: 10.1016/j.cjca.2019.09.019
WAN WEI, ZHOU XIAN-SHUN, CAI HONG-ZHUAN: "Current Status of Research in Dilated Cardiomyopathy Pathogenesis in Ion Channels", ADVANCES IN CARDIOVASCULAR DISEASES, vol. 33, no. 4, 5 July 2012 (2012-07-05), pages 551 - 553, XP055935733, ISSN: 1004-3934, DOI: 10.3969/j.issn.1004-3934.2012.04.037
AIJUN SUN,, LEI XU, SHAOCHUN WANG, KAI HU, CHUNYU ZHANG , ZHIYIN YANG , CHENG SHEN , , KEQIANG WANG , SANLI QIAN , ZHENG FAN ,: "PO-309 Altered Cardiac Sodium Channel Function Due to Voltage-Sensor Mutation in Dilated Cardiomyopathy Patients with SCN5A Mutations", PROCEEDINGS OF THE 15TH SCIENTIFIC ANNUAL CONGRESS OF CHINESE SOCIETY OF CARDIOLOGY, 31 August 2013 (2013-08-31), pages 1 - 1, XP055935737
DAN LU, DAN BAO, WEI DONG, NING LIU, XU ZHANG, SHAN GAO, WENPING GE, XIANG GAO, LIANFENG ZHANG: "Dkk3 prevents familial dilated cardiomyopathy development through Wnt pathway", LABORATORY INVESTIGATION, vol. 96, no. 2, 1 February 2016 (2016-02-01), pages 239 - 248, XP055525827, ISSN: 0023-6837, DOI: 10.1038/labinvest.2015.145
DAI XIYAN , HE WENFENG , CAO LINGLING , ZHOU QIONGQIONG , HONG KUI: "Research progress on the relationship between Wnt/β-catenin signaling pathway and arrhythmogenic right ventricular cardiomyopathy", CHINESE JOURNAL OF CARDIAC PACING AND ELECTROPHYSIOLOGY, vol. 26, no. 6, 12 December 2012 (2012-12-12), pages 476 - 477, XP055935754, ISSN: 1007-2659, DOI: 10.13333/j.cnki.cjcpe.2012.06.009
ABRAITYTE AURELIJA, LUNDE IDA G., ASKEVOLD ERIK T., MICHELSEN ANNIKA E., CHRISTENSEN GEIR, AUKRUST PÅL, YNDESTAD ARNE, FIANE ARNT,: "Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy", SCIENTIFIC REPORTS, vol. 7, no. 1, 1 December 2017 (2017-12-01), pages 1 - 10, XP055935755, DOI: 10.1038/s41598-017-03625-9
LIU, JINGWEN: "Aberrant Expression Profile of mRNA in Dilated Cardiomyopathy by RNA-Sequence", CHINESE JOURNAL OF HEART FAILURE AND CARDIOMYOPATHY, vol. 2, no. 3, 30 September 2018 (2018-09-30), pages 146 - 150, XP009537017, ISSN: 2096-3076, DOI: 10.3760/cma.j.issn.2096-3076.2018.09.004
WAN WEI, ZHOU XIAN-SHUN, CAI HONG-ZHUAN: "Current Status of Research in Dilated Cardiomyopathy Pathogenesis in Ion Channels", ADVANCES IN CARDIOVASCULAR DISEASES, vol. 33, no. 4, 5 July 2012 (2012-07-05), pages 551 - 553, XP055935733, ISSN: 1004-3934, DOI: 10.3969/j.issn.1004-3934.2012.04.037
AIJUN SUN,, LEI XU, SHAOCHUN WANG, KAI HU, CHUNYU ZHANG , ZHIYIN YANG , CHENG SHEN , , KEQIANG WANG , SANLI QIAN , ZHENG FAN ,: "PO-309 Altered Cardiac Sodium Channel Function Due to Voltage-Sensor Mutation in Dilated Cardiomyopathy Patients with SCN5A Mutations", PROCEEDINGS OF THE 15TH SCIENTIFIC ANNUAL CONGRESS OF CHINESE SOCIETY OF CARDIOLOGY, 31 August 2013 (2013-08-31), pages 1 - 1, XP055935737
DAN LU, DAN BAO, WEI DONG, NING LIU, XU ZHANG, SHAN GAO, WENPING GE, XIANG GAO, LIANFENG ZHANG: "Dkk3 prevents familial dilated cardiomyopathy development through Wnt pathway", LABORATORY INVESTIGATION, vol. 96, no. 2, 1 February 2016 (2016-02-01), pages 239 - 248, XP055525827, ISSN: 0023-6837, DOI: 10.1038/labinvest.2015.145
DAI XIYAN , HE WENFENG , CAO LINGLING , ZHOU QIONGQIONG , HONG KUI: "Research progress on the relationship between Wnt/β-catenin signaling pathway and arrhythmogenic right ventricular cardiomyopathy", CHINESE JOURNAL OF CARDIAC PACING AND ELECTROPHYSIOLOGY, vol. 26, no. 6, 12 December 2012 (2012-12-12), pages 476 - 477, XP055935754, ISSN: 1007-2659, DOI: 10.13333/j.cnki.cjcpe.2012.06.009
ABRAITYTE AURELIJA, LUNDE IDA G., ASKEVOLD ERIK T., MICHELSEN ANNIKA E., CHRISTENSEN GEIR, AUKRUST PÅL, YNDESTAD ARNE, FIANE ARNT,: "Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy", SCIENTIFIC REPORTS, vol. 7, no. 1, 1 December 2017 (2017-12-01), pages 1 - 10, XP055935755, DOI: 10.1038/s41598-017-03625-9
LIU, JINGWEN: "Aberrant Expression Profile of mRNA in Dilated Cardiomyopathy by RNA-Sequence", CHINESE JOURNAL OF HEART FAILURE AND CARDIOMYOPATHY, vol. 2, no. 3, 30 September 2018 (2018-09-30), pages 146 - 150, XP009537017, ISSN: 2096-3076, DOI: 10.3760/cma.j.issn.2096-3076.2018.09.004
Attorney, Agent or Firm:
SHANGHAI SHENHUI PATENT AGENT CO., LTD. (CN)
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