Neuromuscular Diseases Unit, Neurology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
Peripheral Nervous System Group, Vall d'Hebron Research Institut (VHIR), Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
Cells. 2023 Apr 18;12(8):1180. doi: 10.3390/cells12081180.
Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons for which effective therapies are lacking. One of the most explored areas of research in ALS is the discovery and validation of biomarkers that can be applied to clinical practice and incorporated into the development of innovative therapies. The study of biomarkers requires an adequate theoretical and operational framework, highlighting the "fit-for-purpose" concept and distinguishing different types of biomarkers based on common terminology. In this review, we aim to discuss the current status of fluid-based prognostic and predictive biomarkers in ALS, with particular emphasis on those that are the most promising ones for clinical trial design and routine clinical practice. Neurofilaments in cerebrospinal fluid and blood are the main prognostic and pharmacodynamic biomarkers. Furthermore, several candidates exist covering various pathological aspects of the disease, such as immune, metabolic and muscle damage markers. Urine has been studied less often and should be explored for its possible advantages. New advances in the knowledge of cryptic exons introduce the possibility of discovering new biomarkers. Collaborative efforts, prospective studies and standardized procedures are needed to validate candidate biomarkers. A combined biomarkers panel can provide a more detailed disease status.
肌萎缩侧索硬化症是一种神经退行性疾病，其特征是运动神经元退化，目前缺乏有效的治疗方法。肌萎缩侧索硬化症研究中最具探索性的领域之一是发现和验证生物标志物，这些生物标志物可以应用于临床实践，并纳入创新疗法的开发中。生物标志物的研究需要一个适当的理论和操作框架，突出“适合目的”的概念，并根据常见术语区分不同类型的生物标志物。在这篇综述中，我们旨在讨论目前基于液体的肌萎缩侧索硬化症预后和预测性生物标志物的现状，特别强调那些最有希望用于临床试验设计和常规临床实践的生物标志物。脑脊液和血液中的神经丝是主要的预后和药效学生物标志物。此外，还有一些候选标志物涵盖了疾病的各种病理方面，如免疫、代谢和肌肉损伤标志物。尿液的研究较少，应该探索其可能的优势。对隐匿外显子的新知识进展引入了发现新生物标志物的可能性。需要协作努力、前瞻性研究和标准化程序来验证候选生物标志物。联合生物标志物面板可以提供更详细的疾病状态。
