肌萎缩侧索硬化症的基因调控治疗方法。
Approaches to Gene Modulation Therapy for ALS.
机构信息
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
出版信息
Neurotherapeutics. 2022 Jul;19(4):1159-1179. doi: 10.1007/s13311-022-01285-w. Epub 2022 Sep 6.
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease for which there is currently no robust therapy. Recent progress in understanding ALS disease mechanisms and genetics in combination with innovations in gene modulation strategies creates promising new options for the development of ALS therapies. In recent years, six gene modulation therapies have been tested in ALS patients. These target gain-of-function pathology of the most common ALS genes, SOD1, C9ORF72, FUS, and ATXN2, using adeno-associated virus (AAV)-mediated microRNAs and antisense oligonucleotides (ASOs). Here, we review the latest clinical and preclinical advances in gene modulation approaches for ALS, including gene silencing, gene correction, and gene augmentation. These techniques have the potential to positively impact the direction of future research trials and transform ALS treatments for this grave disease.
摘要
肌萎缩侧索硬化症（ALS）是一种毁灭性的运动神经元疾病，目前尚无有效的治疗方法。目前对 ALS 疾病机制和遗传学的深入了解，结合基因调控策略的创新，为 ALS 治疗的发展带来了有希望的新选择。近年来，已有六种基因调控疗法在 ALS 患者中进行了测试。这些疗法针对最常见的 ALS 基因 SOD1、C9ORF72、FUS 和 ATXN2 的功能获得性病理学，使用腺相关病毒（AAV）介导的 microRNAs 和反义寡核苷酸（ASO）。在这里，我们回顾了 ALS 基因调控方法的最新临床和临床前进展，包括基因沉默、基因矫正和基因增强。这些技术有可能对未来的研究试验产生积极影响，并改变这种严重疾病的治疗方法。
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