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亨廷顿病的免疫疗法是否现实?

Are immunotherapies for Huntington's disease a realistic option?

机构信息

Centre de Recherche du CHU de Québec, Université Laval, Québec, QC, G1V 4G2, Canada.

Département de Psychiatrie & Neurosciences, Université Laval, Québec, QC, G1V 0A6, Canada.

出版信息

Mol Psychiatry. 2019 Mar;24(3):364-377. doi: 10.1038/s41380-018-0021-9. Epub 2018 Feb 27.

Abstract

There is compelling evidence that the pathophysiology of many neurodegenerative diseases includes dysregulation of the immune system, with some elements that precede disease onset. However, if these alterations are prominent, why have clinical trials targeting this system failed to translate into long-lasting meaningful benefits for patients? This review focuses on Huntington's disease, a genetic disorder marked by notable cerebral and peripheral inflammation. We summarize ongoing and completed clinical trials that have involved pharmacological approaches to inhibit various components of the immune system and their pre-clinical correlates. We then discuss new putative treatment strategies using more targeted immunotherapies such as vaccination and intrabodies and how these may offer new hope in the treatment of Huntington's disease as well as other neurodegenerative diseases.

摘要

有确凿的证据表明,许多神经退行性疾病的病理生理学包括免疫系统的失调,其中一些因素发生在疾病发作之前。然而,如果这些改变很明显,为什么针对该系统的临床试验未能为患者带来持久的有意义的益处?本综述重点关注亨廷顿病,这是一种遗传性疾病,其特征是明显的大脑和外周炎症。我们总结了正在进行和已完成的临床试验,这些试验涉及药理学方法来抑制免疫系统的各种成分及其临床前相关性。然后,我们讨论了使用更靶向的免疫疗法(如疫苗接种和内抗体)的新的假定治疗策略,以及这些策略如何为亨廷顿病和其他神经退行性疾病的治疗带来新的希望。

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