Enabling advances in diagnosis, patient stratification and treatment for dilated cardiomyopathy patients and families (DCM Next)

促进扩张型心肌病患者和家庭的诊断、患者分层和治疗取得进展 (DCM Next)

• 批准号: 10085929
• 金额: $ 38.83万
• 依托单位: IMPERIAL COLLEGE LONDON
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10085929
• 关键词: Enabling; advances; diagnosis; patient; stratification

Dilated Cardiomyopathy (DCM) is a heart muscle disorder characterised by thinning and stretching of the heart ventricles, making it harder for the heart to pump blood (systolic dysfunction). This disorder, with an estimated prevalence of up to 1/250, predominantly affects younger adults. It is associated with significant morbidity and mortality, including heart failure and sudden cardiac death, with end-stage DCM being the leading indication for heart transplantation. The current disease burden in DCM is largely attributable to two important gaps in scientific knowledge: Firstly, our understanding of the aetiology and genetic architecture of DCM remains limited, hindering the utility of genetic testing in clinical patient management. Secondly, there are limited therapeutic options for DCM patients. Existing therapies are generic and target symptoms. No curative treatments exist, apart from invasive heart transplantation and there are no approved therapiestargeting underlying molecular disease mechanisms. A fuller understanding of the genetic architecture of DCM and knowledge of the genes and genetic variants involved are critically needed to provide solutions for these unmet medical needs. The DCM NEXT consortium combines world-leading interdisciplinary expertise and resources of 8 investigators in the fields of DCM, deep clinical phenotyping, cardiogenomics, cardiac transcriptomics, artificial intelligence, in silico drug target discovery and functional studies. They will uniquely leverage their unparalleled cohort of 11,750 DCM probands and relatives with extensive clinical and omics data. Through cutting-edge genomic and cardiac transcriptomic studies, the project aims to (1) revolutionise genetic testing and patient stratification for more precise prediction of disease onset, progression and risk of major adverse cardiac events; and (2) accelerate development of novel therapies by identifying and validating targets involved in pathogenesis of DCM.

扩张型心肌病 (DCM) 是一种心肌疾病，其特征是心室变薄和拉伸，使心脏泵血变得更加困难（收缩功能障碍）。这种疾病的患病率估计高达 1/250，主要影响年轻人。它与显着的发病率和死亡率相关，包括心力衰竭和心源性猝死，而终末期 DCM 是心脏移植的主要适应症。当前DCM的疾病负担很大程度上归因于科学知识上的两个重要差距：首先，我们对DCM的病因学和遗传结构的理解仍然有限，阻碍了基因检测在临床患者管理中的实用性。其次，DCM 患者的治疗选择有限。现有的疗法是通用的和针对症状的。除了侵入性心脏移植外，不存在治愈性治疗方法，也没有针对潜在分子疾病机制的批准疗法。迫切需要更全面地了解扩张型心肌病的遗传结构以及所涉及的基因和遗传变异的知识，才能为这些未满足的医疗需求提供解决方案。 DCM NEXT 联盟结合了 DCM、深度临床表型分析、心脏基因组学、心脏转录组学、人工智能、计算机模拟药物靶标发现和功能研究领域的 8 位研究人员的世界领先的跨学科专业知识和资源。他们将独特地利用由 11,750 名 DCM 先证者和亲属组成的无与伦比的队列，以及广泛的临床和组学数据。通过尖端的基因组和心脏转录组学研究，该项目旨在（1）彻底改变基因检测和患者分层，以更准确地预测疾病的发作、进展和主要不良心脏事件的风险； (2) 通过识别和验证 DCM 发病机制中涉及的靶点来加速新疗法的开发。