Disease heterogeneity in amyotrophic lateral sclerosis poses a substantial challenge in drug development. Categorization based on clinical features alone can help us predict the disease course and survival, but quantitative measures are also needed that can enhance the sensitivity of the clinical categorization. In this Review, we describe the emerging landscape of diagnostic, categorical and pharmacodynamic biomarkers in amyotrophic lateral sclerosis and their place in the rapidly evolving landscape of new therapeutics. Fluid-based markers from cerebrospinal fluid, blood and urine are emerging as useful diagnostic, pharmacodynamic and predictive biomarkers. Combinations of imaging measures have the potential to provide important diagnostic and prognostic information, and neurophysiological methods, including various electromyography-based measures and quantitative EEG–magnetoencephalography-evoked responses and corticomuscular coherence, are generating useful diagnostic, categorical and prognostic markers. Although none of these biomarker technologies has been fully incorporated into clinical practice or clinical trials as a primary outcome measure, strong evidence is accumulating to support their clinical utility.

肌萎缩侧索硬化症的疾病异质性对药物开发提出了巨大的挑战。仅基于临床特征的分类可以帮助我们预测病程和生存，但还需要定量措施来提高临床分类的敏感性。在这篇综述中，我们描述了肌萎缩侧索硬化症诊断、分类和药效生物标志物的新兴前景及其在快速发展的新疗法中的地位。来自脑脊液、血液和尿液的液体标记物正在成为有用的诊断、药效和预测生物标记物。成像测量的组合有可能提供重要的诊断和预后信息，神经生理学方法，包括各种基于肌电图的测量和定量脑电图-脑磁图诱发的反应和皮质肌肉一致性，正在产生有用的诊断、分类和预后标记。尽管这些生物标志物技术尚未完全纳入临床实践或临床试验作为主要结果衡量标准，但强有力的证据正在积累以支持其临床实用性。