Turner Martin R, Kiernan Matthew C, Leigh P Nigel, Talbot Kevin
Department of Clinical Neurology, University of Oxford, Oxford, UK.
Lancet Neurol. 2009 Jan;8(1):94-109. doi: 10.1016/S1474-4422(08)70293-X.
Amyotrophic lateral sclerosis (ALS; motor neuron disease) is a relentlessly progressive disorder. After half a century of trials, only one drug with modest disease-modifying potency--riluzole--has been developed. The diagnosis of this disorder is still clinical and there is a pronounced delay between the onset of symptoms and diagnosis, possibly beyond the therapeutic window. Bedside quantification of the involvement of the corticospinal tract and extramotor areas is inadequate and functional rating scales, forced vital capacity, and patient survival have been the measures of therapeutic response so far. Potential biomarkers that are sensitive to the progression of disease, which might enhance the diagnostic algorithm and provide new drug targets, are now being identified from analysis of the blood and cerebrospinal fluid, as well as from neuroimaging and neurophysiology studies. In combination, these biomarkers might be sensitive to early therapeutic effects and would reduce our reliance on animal models, which have uncertain relevance to sporadic ALS in human beings. Such biomarkers might also resolve complexities of phenotypic heterogeneity in clinical trials. In this Review, we discuss the development of biomarkers in ALS and consider potential future directions for research.
肌萎缩侧索硬化症（ALS；运动神经元病）是一种无情进展的疾病。经过半个世纪的试验，仅开发出一种具有适度疾病修饰效力的药物——利鲁唑。该疾病的诊断仍基于临床，症状出现与诊断之间存在明显延迟，可能超出了治疗窗。床边对皮质脊髓束和运动外区域受累情况的量化不足，迄今为止，功能评定量表、用力肺活量和患者生存率一直是治疗反应的衡量指标。目前正在通过血液和脑脊液分析以及神经影像学和神经生理学研究，鉴定对疾病进展敏感的潜在生物标志物，这些生物标志物可能会改进诊断算法并提供新的药物靶点。综合起来，这些生物标志物可能对早期治疗效果敏感，并将减少我们对动物模型的依赖，动物模型与人类散发性ALS的相关性尚不确定。此类生物标志物还可能解决临床试验中表型异质性的复杂性。在本综述中，我们讨论了ALS生物标志物的发展，并考虑了未来潜在的研究方向。
