Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
WPI -Immunology Frontier Research Center, Osaka University, Suita, Japan.
Front Immunol. 2020 Feb 25;11:337. doi: 10.3389/fimmu.2020.00337. eCollection 2020.
Modulation of immune activation using immunotherapy has attracted considerable attention for many years as a potential therapeutic intervention for several inflammation-associated neurodegenerative diseases. However, the efficacy of single-target immunotherapy intervention has shown limited or no efficacy in alleviating disease burden and restoring functional capacity. Marked immune system activation and neuroinflammation are important features and prodromal signs in polyQ repeat disorders and α-synucleinopathies. This review describes the current status and future directions of immunotherapies in proteinopathy-induced neurodegeneration with emphasis on preclinical and clinical efficacies of several anti-inflammatory compounds and antibody-based therapies for the treatment of Huntington's disease and α-synucleinopathies. The review concludes with how disease modification and functional restoration could be achieved by using targeted multimodality therapy to target multiple factors.
多年来,免疫疗法通过调节免疫激活引起了人们的极大关注,被认为是治疗多种与炎症相关的神经退行性疾病的潜在治疗方法。然而,单一靶点免疫治疗干预在减轻疾病负担和恢复功能能力方面的疗效有限或无效。明显的免疫系统激活和神经炎症是多聚谷氨酰胺重复疾病和α-突触核蛋白病的重要特征和前驱症状。本文描述了蛋白质病诱导的神经退行性变中免疫治疗的现状和未来方向,重点介绍了几种抗炎化合物和抗体治疗方法在治疗亨廷顿病和α-突触核蛋白病方面的临床前和临床疗效。本文最后讨论了如何通过靶向多种因素的靶向多模态治疗来实现疾病的修饰和功能的恢复。