Lydia Castelli, Rosario Vasta, Scott P Allen, Rachel Waller, Adriano Chiò, Bryan J Traynor, Janine Kirby
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引用次数: 0
摘要
肌萎缩性脊髓侧索硬化症(ALS)是一种异质性进行性神经退行性疾病,利鲁唑和依达拉奉等现有疗法可将患者的生存期平均延长 3-6 个月。缺乏高效、广泛可用的疗法反映了 ALS 的复杂性。包括基因组学、转录组学和蛋白质组学在内的 Omics 技术有助于确定临床前和临床试验中治疗策略所针对的失调生物通路。将临床、环境和神经影像学信息与全局组学数据相结合,并应用系统生物学方法,可以进一步提高我们对该疾病的认识,从而有可能对患者进行分层,并提供更加个性化的医疗服务。本章将回顾有助于采用系统生物学方法的 omics 技术,以及这些组成部分如何帮助确定治疗目标。本章还将讨论当前的策略,包括在临床试验中使用基因筛选和生物取样,以及未来应用其他先进技术的情况。
From use of omics to systems biology: Identifying therapeutic targets for amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a heterogeneous progressive neurodegenerative disorder with available treatments such as riluzole and edaravone extending survival by an average of 3-6 months. The lack of highly effective, widely available therapies reflects the complexity of ALS. Omics technologies, including genomics, transcriptomic and proteomics have contributed to the identification of biological pathways dysregulated and targeted by therapeutic strategies in preclinical and clinical trials. Integrating clinical, environmental and neuroimaging information with omics data and applying a systems biology approach can further improve our understanding of the disease with the potential to stratify patients and provide more personalised medicine. This chapter will review the omics technologies that contribute to a systems biology approach and how these components have assisted in identifying therapeutic targets. Current strategies, including the use of genetic screening and biosampling in clinical trials, as well as the future application of additional technological advances, will also be discussed.