Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081 Ulm, Germany.
Curr Opin Neurol. 2012 Oct;25(5):530-5. doi: 10.1097/WCO.0b013e328356d328.
The field of amyotrophic lateral sclerosis (ALS) has seen a number of remarkable advances during recent years that will be summarized in this review.
In particular, the progress in the molecular neuropathology with the discovery of pathogenic mutations in TAR DNA binding protein (TARDBP), fused in sarcoma (FUS), ubiquilin2 (UBQLN2) and most recently C9ORF72 (abbreviation for the open reading frame 72 on chromosome 9) has further substantiated the - clinically temporarily forgotten - relation of classic ALS to frontotemporal degeneration (FTD). Also, major progress has been made by the discovery of genes relevant for the disease, and pathogenetic concepts have been suggested which imply that not one, but multiple genetic and cell biological hits are involved in the causation of the disease. Progress in interventional therapies has remained poor; important recent examples are the failure of the interventional lithium and pioglitazone trials. However, a study of a third interventional compound - dexpramipexol - raises substantial hopes that the class of chemicals originally represented by riluzole - benzothiazoles - may provide additional therapeutic progress for ALS patients.
Tremendous progress has been made in the field of ALS based on recent neuropathological and genetic discoveries. Moreover, the role of metabolism and nutrition in the pathogenesis of the disease is debated and may potentially serve as a future therapeutic target. For the facilitation and cost reduction of clinical trials, the development and international standardization of disease-specific 'wet' and 'dry' biomarkers is essential.
近年来，肌萎缩侧索硬化症（ALS）领域取得了许多显著进展，本综述对此进行了总结。
特别是在分子神经病理学方面取得了进展，发现了 TAR DNA 结合蛋白（TARDBP）、肉瘤融合（FUS）、泛素结合蛋白 2（UBQLN2）和最近的 C9ORF72（9 号染色体开放阅读框 72 的缩写）的致病性突变，进一步证实了经典 ALS 与额颞叶变性（FTD）之间的临床暂时被遗忘的关系。此外，通过发现与疾病相关的基因取得了重大进展，并提出了发病机制概念，这意味着不是一个而是多个遗传和细胞生物学因素参与了疾病的发生。干预治疗的进展仍然很差；最近的重要例子是干预锂和吡格列酮试验的失败。然而，一项对第三种干预化合物——右旋普瑞巴林的研究，为一类最初以利鲁唑为代表的化学物质——苯并噻唑类，可能为 ALS 患者提供额外的治疗进展带来了巨大的希望。
基于最近的神经病理学和遗传学发现，ALS 领域取得了巨大进展。此外，代谢和营养在疾病发病机制中的作用正在被讨论，并且可能成为未来的治疗靶点。为了促进临床试验的开展和降低成本，开发和制定疾病特异性的“湿”和“干”生物标志物的国际标准是至关重要的。
