Sheffield Institute for Translational Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom.
ALS Expert Center,'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy; Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States.
Int Rev Neurobiol. 2024;176:209-268. doi: 10.1016/bs.irn.2024.02.001. Epub 2024 May 22.
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.
肌萎缩侧索硬化症（ALS）是一种异质性进行性神经退行性疾病，目前已有利鲁唑和依达拉奉等治疗方法，可将平均生存期延长 3-6 个月。缺乏高疗效、广泛可用的治疗方法反映了 ALS 的复杂性。组学技术，包括基因组学、转录组学和蛋白质组学，有助于确定临床前和临床试验中受治疗策略调节和靶向的生物学途径。将临床、环境和神经影像学信息与组学数据整合，并应用系统生物学方法，可以进一步提高我们对疾病的认识，有可能对患者进行分层，并提供更个性化的治疗。本章将回顾有助于系统生物学方法的组学技术，以及这些成分如何帮助确定治疗靶点。还将讨论当前的策略，包括在临床试验中使用遗传筛选和生物样本，以及未来应用其他技术进步。
