Abstract：
Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets. In this review, we focus on Friedreich ataxia (FRDA) and the polyglutamine ataxias in which translational research is active. However, much remains to be done to identify safe and effective molecules, create ideal delivery methods, and perform innovative clinical trials to prove the safety and efficacy of treatments for these rare but devastating diseases.
摘要：
最近的研究已经确定了许多遗传性共济失调（HAs）的病理生理基础，包括RNA或蛋白质水平的功能丧失和功能获得机制。临床前研究已经评估了基因编辑，基因和蛋白质替代，基因增强，和基因敲除策略。方法包括病毒载体递送基因，寡核苷酸疗法，细胞穿透肽，合成转录因子，以及为定义的目标提供治疗的技术。在这次审查中,我们专注于Friedreich共济失调（FRDA）和翻译研究活跃的聚谷氨酰胺共济失调。然而,要确定安全有效的分子还有很多工作要做，创造理想的交付方式，并进行创新的临床试验，以证明这些罕见但破坏性疾病的治疗方法的安全性和有效性。
