公开(公告)号：EP2736516A1

公开(公告)日：2014-06-04

申请号：EP12811596.1

申请日：2012-07-13

申请人： Icahn School of Medicine at Mount Sinai

发明人： HAJJAR, Roger, Joseph ,  KHO, Chang, Won ,  LEE, Ah, Young

IPC分类号： A61K31/7088 ,  C12N15/11 ,  C12N15/113

CPC分类号： A61K38/50 ,  A61K31/7088 ,  A61K38/1709 ,  A61K48/0066 ,  C12N7/00 ,  C12N15/86 ,  C12N2750/14143 ,  C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  C12Y305/00 ,  G01N33/573 ,  G01N2333/914 ,  G01N2440/36 ,  G01N2800/325

摘要： Methods for treating cardiovascular disease, and in particular heart failure, are provided comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translation modification such as SUMOylation or acetylation. Also provided are methods of treating cardiovascular disease by inhibiting SERCA2a degradation. Further provided are methods of diagnosing a propensity to develop heart failure comprising determining if a SERCA2a mutant is present or determining the level of expression of SUMOl in cardiomyocytes. The disclosure also provides methods of screening for therapeutics that modulate the post-translational modification of SERCA2a, such as by modulating post-translational SUMOylation and/or acetylation.

摘要翻译： 提供了治疗心血管疾病，特别是心力衰竭的方法，包括施用治疗有效量的SERCA2a翻译后修饰调节剂，例如SUMO化或乙酰化。 还提供了通过抑制SERCA2a降解来治疗心血管疾病的方法。 进一步提供了诊断发展为心力衰竭倾向的方法，包括确定SERCA2a突变体是否存在或确定SUMO1在心肌细胞中的表达水平。 本公开还提供筛选调节SERCA2a的翻译后修饰的治疗剂的方法，例如通过调节翻译后SUMO化和/或乙酰化。