Mitsumoto Hiroshi, Saito Toyokazu
Wesley J Howe Professor of Neurology (at CUMC), Eleanor and Lou Gehrig ALS Center, Department of Neurology, Columbia University Medical Center (CUMC).
Emeritus professor, Kitasato University.
Rinsho Shinkeigaku. 2018 Dec 21;58(12):729-736. doi: 10.5692/clinicalneurol.cn-001220. Epub 2018 Nov 29.
Although we currently have two, approved, disease-modifying drugs for the treatment of amyotrophic lateral sclerosis (ALS), we are in disperate need for more efficacious treatment. To aggressively test for newer therapies, we must develop reliable objective biomarkers to supplement clinical outcome measures. Many biomarker candidates have been actively and vigorously investigated. Among neurophysiological biomarkers, transcranial magnetic stimulation (TMS)-based biomarkers show potential in exploring disease mechanisms. Neuroimaging biomarkers have high specificity in diagnosing ALS but are an expensive endeavor and are not sensitive enough to detect changes over time of the disease. Among fluid-based biochemical biomarkers, creatinine (Crn) and uric acids (UA), which have been known for decades, may prove to be highly promising biomarkers that can predict disease progression. They can be easily tested in any clinical trials because the costs are minimal. Although known for some time, neurofilaments (NF), either phosphorylated-NF heavy subunit (pNFH) or NF light subunit (NFL), have emerged as "new" biomarkers using specific antibodies. They appear to be highly specific and sensitive in diagnosing ALS, yet they may be insensitive to assess changes in disease over time. These two NF biomarkers along with Crn and UA should be explored extensively in future clinical trials and any other clinical studies in ALS. Yet, we still need newer, more innovative, and reliable biomarkers for future ALS research. Fortunatley, aggressive investigations appear to be currently underway.
尽管目前我们有两种已获批的用于治疗肌萎缩侧索硬化症（ALS）的疾病修饰药物，但我们迫切需要更有效的治疗方法。为了积极测试新的疗法，我们必须开发可靠的客观生物标志物来补充临床结局指标。许多生物标志物候选物已经得到积极且深入的研究。在神经生理学生物标志物中，基于经颅磁刺激（TMS）的生物标志物在探索疾病机制方面显示出潜力。神经影像学生物标志物在诊断ALS方面具有高特异性，但成本高昂，且对检测疾病随时间的变化不够敏感。在基于体液的生化生物标志物中，已为人所知数十年的肌酐（Crn）和尿酸（UA）可能被证明是极具前景的、能够预测疾病进展的生物标志物。它们可以在任何临床试验中轻松检测，因为成本极低。虽然神经丝（NF），无论是磷酸化神经丝重链亚基（pNFH）还是神经丝轻链亚基（NFL），已经为人所知一段时间了，但使用特异性抗体后，它们已成为“新”的生物标志物。它们在诊断ALS方面似乎具有高度特异性和敏感性，但可能对评估疾病随时间的变化不敏感。这两种NF生物标志物以及Crn和UA应在未来的ALS临床试验和任何其他临床研究中进行广泛探索。然而，我们仍然需要更新颖、更具创新性和更可靠的生物标志物用于未来的ALS研究。幸运的是，目前似乎正在进行积极的研究。
