Centre for Clinical Research, The University of Queensland , Brisbane, Australia.
Department of Neurology, Royal Brisbane and Women's Hospital , Brisbane, Australia.
Expert Rev Neurother. 2020 Sep;20(9):921-941. doi: 10.1080/14737175.2020.1785873. Epub 2020 Aug 7.
ALS is a fatal neurodegenerative disease. However, patients show variability in the length of survival after symptom onset. Understanding the mechanisms of long survival could lead to possible avenues for therapy.
This review surveys the reported length of survival in ALS, the clinical features that predict survival in individual patients, and possible factors, particularly genetic factors, that could cause short or long survival. The authors also speculate on possible mechanisms.
a small number of known factors can explain some variability in ALS survival. However, other disease-modifying factors likely exist. Factors that alter motor neurone vulnerability and immune, metabolic, and muscle function could affect survival by modulating the disease process. Knowing these factors could lead to interventions to change the course of the disease. The authors suggest a broad approach is needed to quantify the proportion of variation survival attributable to genetic and non-genetic factors and to identify and estimate the effect size of specific factors. Studies of this nature could not only identify novel avenues for therapeutic research but also play an important role in clinical trial design and personalized medicine.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病。然而，患者在症状出现后的生存时间存在差异。了解导致长期生存的机制可能为治疗提供新途径。
本文综述了 ALS 患者报告的生存时间、个体患者生存预测的临床特征，以及可能导致短或长生存时间的潜在因素，特别是遗传因素。作者还对可能的机制进行了推测。
少数已知因素可以解释 ALS 生存时间的一些差异。然而，可能存在其他疾病修饰因素。改变运动神经元易损性以及免疫、代谢和肌肉功能的因素可能通过调节疾病进程来影响生存。了解这些因素可能会导致干预措施改变疾病进程。作者建议需要采用广泛的方法来量化遗传和非遗传因素对生存差异的贡献，并确定和估计特定因素的效应大小。开展此类研究不仅可以为治疗研究开辟新途径，而且还可以在临床试验设计和个体化医学中发挥重要作用。
