Bowser Robert, Cudkowicz Merit, Kaddurah-Daouk Rima
University of Pittsburgh, Department of Pathology, School of Medicine, ST S-420, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Expert Rev Mol Diagn. 2006 May;6(3):387-98. doi: 10.1586/14737159.6.3.387.
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease. ALS is a fatal neurodegenerative disease and clinical diagnosis typically takes many months to complete. Early disease diagnosis through the use of biomarkers may aid in correct clinical management of patients and possibly delay time to ventilator and morbidity. This review explores the progress of biomarker discovery efforts for ALS and the many challenges that remain. Included are different technologies utilized in biomarker discovery efforts (proteomic, genomic and metabolomic) and putative biomarkers uncovered using these techniques. These studies have discovered genetic mutations leading to familial forms of ALS, and specific protein alterations that occur in biological fluids (cerebrospinal fluid and blood) and/or tissues of ALS subjects. More recent high-throughput technologies have revealed panels of proteomic or metabolic biomarkers that can discriminate between ALS and control groups. The identification of disease-specific biomarkers will provide opportunities to develop early diagnostic measures as well as surrogate markers to monitor disease progression and test drug efficacy in clinical trials.
肌萎缩侧索硬化症（ALS）是运动神经元疾病最常见的形式。ALS是一种致命的神经退行性疾病，临床诊断通常需要数月才能完成。通过使用生物标志物进行疾病早期诊断，可能有助于对患者进行正确的临床管理，并有可能延迟使用呼吸机的时间和降低发病率。本综述探讨了ALS生物标志物发现工作的进展以及仍然存在的诸多挑战。其中包括生物标志物发现工作中使用的不同技术（蛋白质组学、基因组学和代谢组学）以及使用这些技术发现的假定生物标志物。这些研究发现了导致家族性ALS的基因突变，以及在ALS患者的生物体液（脑脊液和血液）和/或组织中发生的特定蛋白质改变。最近的高通量技术已经揭示了能够区分ALS组和对照组的蛋白质组或代谢生物标志物面板。疾病特异性生物标志物的识别将为开发早期诊断措施以及替代标志物提供机会，以监测疾病进展并在临床试验中测试药物疗效。
