写的:
Head of Bioscience Cardiovascular, Early CVRM, AstraZeneca
Head of Translational Sciences and Experimental Medicine, Early CVRM, AstraZeneca
能够精确地定位心衰个体疾病的潜在分子原因，将是当前主要依赖临床体征和症状的临床管理范式的根本改变. 对心力衰竭基因驱动因素的日益深入的了解正在为以下研究奠定基础 precision medicine in what is a highly heterogeneous disease affecting 64 million people worldwide.1
在澳门葡京网赌游戏, 澳门葡京赌博游戏正在与世界领先的专家合作，确定新的靶点和生物标志物，以发现和开发针对危及生命的心肌疾病的精准医学, 如缺血性心肌病(ICM)和特发性扩张型心肌病(IDCM)和遗传性肌肉萎缩症, Duchenne muscular dystrophy (DMD).
Identifying molecular fingerprints of 心脏衰竭
By harnessing the power of artificial intelligence and omics analysis, our aim is to unravel the complex disease biology of 心脏衰竭 at the molecular level in individual patients. 澳门葡京赌博游戏正在使用机器学习来分析来自心脏活检样本的大量基因表达数据，并将心力衰竭患者分层为新的分子亚类, irrespective of their clinical signs and symptoms. 这些见解揭示了这些同质亚类患者共享的“分子指纹”与心力衰竭诊断中通常使用的ICM和IDCM分类无关. 澳门葡京赌博游戏开始将亚类特异性基因表达谱与失调的分子途径和过程联系起来，这些分子途径和过程指示着不同亚类的不同疾病生物学. We are also using gene expression data from past trials, linked with clinical data, to see whether they actually correspond to clinically meaningful phenotypes. Using all this new information, 澳门葡京赌博游戏计划确定新的治疗靶点，这将形成精准医学方法的基础，以治疗不同分子亚类心力衰竭患者.
Targeting impaired heart muscle contraction
扩张型心肌病(DCM)中心肌拉伸和减弱的遗传驱动因素之一是磷蛋白(PLN)基因的突变。, a key protein for cellular calcium regulation. 过度的PLN活动与钙循环缺陷和心肌收缩和松弛受损有关. Whilst a key target for drug discovery, so far the structure of the protein has proved hard to target with conventional drugs.
Encouraging laboratory data have demonstrated the potential of antisense oligonucleotides (ASOs) to target PLN activity in DCM.2 研究, 该研究是与Ionis制药公司以及格罗宁根大学医学中心和卡罗林斯卡研究所的国际心力衰竭科学家合作进行的, 研究表明，ASOs——合成DNA链——可以用来消耗与DCM相连的PLN的形成.
In a preclinical model encoding the PLN R14 基因缺失时，澳门葡京赌博游戏使用ASOs降低PLN活性，预防心功能障碍，提高生存率.2 We also saw encouraging results with ASOs in other 心脏衰竭 models, 使其成为治疗心肌病和其他形式心力衰竭的精准医疗方法.
Gene editing in DMD
在出生时患有DMD的儿童护理方面取得的进展改善了患有这种疾病的人的前景, 但心肌的进行性消耗会导致限制生命的DCM和心力衰竭，当人们到了20多岁.
Progress with gene therapy that targets the heart muscle has been limited.3 However, using our well established CRISPR-Cas9 gene editing expertise, our teams are investigating the removal of faulty sequences from the dystrophin gene, 并使用腺相关病毒有效地向心肌细胞提供靶向治疗. 如果这种方法有效，那么也有可能将这种方法扩展到其他遗传性疾病.
Learning from rare genetic drivers of 心脏衰竭
通过对心力衰竭的基因驱动因素的深入研究，澳门葡京赌博游戏的目标是进一步了解为什么一些基因突变的患者会患上这种疾病，而另一些则不会.
In a recent collaboration, 澳门葡京赌博游戏基因组学研究中心的科学家发现，心肌病基因中罕见变异的频率有所增加, TTN, among 5000 people with 心脏衰竭 compared to over 13,000 healthy individuals.4 除了, variants were found in 21 different genes linked to cardiomyopathy, 无论患者是否患有心力衰竭并保留或降低射血分数-该疾病的主要临床类别. 这意味着, although patients may go to their doctor with different symptoms, their underlying genetic drivers may be similar, with environment and comorbidities playing a bigger role than previously thought.
Right patient, right drug, right time
By exploring subtle genetic mutations, 在更常见的心衰形式中基因表达和基因-环境相互作用的变异, 有可能对患者进行分层，以进行生物标志物引导的靶向治疗的临床试验. Drawing on innovations in clinical trial design, 利用不断扩展的新型药物模式工具包，澳门葡京赌博游戏的目标是针对心力衰竭中几乎任何类型的潜在疾病生物学，以便在正确的时间为正确的患者提供正确的药物.
