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.

扩张的心肌病（DCM）是一种心脏肌肉疾病，其特征是心室心室变薄和伸展，使心脏更难泵血（收缩功能障碍）。这种疾病估计患病率高达1/250，主要影响年轻人。它与明显的发病率和死亡率有关，包括心力衰竭和心脏猝死，终末期DCM是心脏移植的主要指标。 DCM中当前的疾病负担在很大程度上归因于科学知识中的两个重要差距：首先，我们对DCM的病因和遗传结构的理解仍然有限，这阻碍了临床患者管理中基因检测的实用性。其次，DCM患者的治疗选择有限。现有疗法是通用症状和靶向症状。除了侵入性的心脏移植外，没有治疗性治疗，并且没有批准的治疗方法基础分子疾病机制。需要对DCM的遗传结构以及所涉及的基因和遗传变异的知识进行更深入的了解，以满足这些未满足的医疗需求的解决方案。 DCM Next Consortium结合了DCM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，深层临床表型，心脏基因组学，心脏转录组学，人工智能，在硅药物目标发现和功能研究中。他们将独特地利用他们的无与伦比的11,750个DCM概率和亲戚的无与伦比的队列，并具有广泛的临床和OMICS数据。通过尖端的基因组和心脏转录组研究，该项目的目的是（1）革新基因检测和患者分层，以更精确地预测疾病发作，进展和重大不良心脏事件的风险； （2）通过识别和验证与DCM发病机理有关的靶标加速新疗法的发展。