Faculté de Médecine, Université Laval, Québec, GIV OA6, Canada.
Département de Médecine, Centre Hospitalier Universitaire de Québec, Québec, Canada.
CNS Neurol Disord Drug Targets. 2023;22(5):678-697. doi: 10.2174/1871527321666220418114846.
The autosomal recessive cerebellar ataxias (ARCAs) compose a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by prominent cerebellar ataxia, dysmetria, dysarthria, and nystagmus that are inherited in an autosomal recessive fashion. The diagnosis of ARCAs is challenging because of their low prevalence, poor medical recognition, and heterogeneous clinical presentation with many overlapping features between entities. There currently exist no disease-modifying therapies for most ARCAs, and treatment is mainly symptomatic, aimed at prolonging independence and maintaining the quality of life. As knowledge of the common pathogenic pathways underlying several ARCAs grows, so do these pathways to target with new drugs. Chelation or enzyme replacement therapies are available for some specific ataxias caused by amenable metabolic alterations. A large number of drug trials are ongoing and aim to identify new therapeutic approaches to expand the options in our repertoire. Improved protocols of motor rehabilitation and noninvasive cerebellar stimulation have been shown to delay disease progression and maintain quality of life. Furthermore, recent progress in gene and molecular targeting therapies is rapidly expanding and holds promise for repairing defective genes. Neurotransplantation of grafted stem cells, which is still at the experimental preclinical stage, has opened new therapeutic strategies aimed at delaying cell degeneration and facilitating compensatory functions. This article is an overview of the current management and treatment strategies with an emphasis on promising perspectives for patients with ARCAs.
常染色体隐性小脑共济失调（ARCA）是一组临床和遗传上具有异质性的神经退行性疾病，其特征为显著的小脑共济失调、运动失调、构音障碍和眼球震颤，呈常染色体隐性遗传方式。由于其发病率低、医学认知度差以及临床表现异质性大，许多疾病实体之间存在许多重叠特征，因此 ARCA 的诊断具有挑战性。目前，大多数 ARCA 没有改变疾病进程的治疗方法，治疗主要是对症治疗，旨在延长独立性和维持生活质量。随着对几种 ARCA 共同发病机制途径的了解不断增加，针对这些途径的新药物治疗方法也在不断增加。对于某些由可治疗代谢改变引起的特定共济失调，可采用螯合或酶替代疗法。目前正在进行大量药物试验，旨在确定新的治疗方法，以扩大我们治疗方案的选择。已证明改进的运动康复和非侵入性小脑刺激方案可延缓疾病进展并维持生活质量。此外，基因和分子靶向治疗的最新进展正在迅速扩大，并有望修复有缺陷的基因。移植干细胞的神经移植仍处于实验性临床前阶段，为旨在延缓细胞退化和促进代偿功能的新治疗策略开辟了道路。本文概述了目前的管理和治疗策略，重点介绍了 ARCA 患者有希望的前景。
