Autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) is an early‐onset neurodegenerative disease that includes progressive cerebellar dysfunction. ARSACS is caused by an autosomal recessive loss‐of‐function mutation in the SACS gene, which encodes for SACSIN. Although animal models are still necessary to investigate the role of SACSIN in the pathology of this disease, more reliable human cellular models need to be generated to better understand the cerebellar pathophysiology of ARSACS. The discovery of human induced pluripotent stem cells (hiPSC) has permitted the derivation of patient‐specific cells. These cells have an unlimited self‐renewing capacity and the ability to differentiate into different neural cell types, allowing studies of disease mechanism, drug discovery and cell replacement therapies. In this study, we discuss how the hiPSC‐derived cerebellar organoid culture offers novel strategies for targeting the pathogenic mutations related to ARSACS. We also highlight the advantages and challenges of this 3D cellular model, as well as the questions that still remain unanswered.

中文翻译：

---

调查 ARSACS：了解小脑变性的模型

Charlevoix-Saguenay 常染色体隐性痉挛性共济失调 (ARSACS) 是一种早发性神经退行性疾病，包括进行性小脑功能障碍。ARSACS 是由编码 SACSIN 的 SACS 基因中的常染色体隐性功能丧失突变引起的。尽管仍然需要动物模型来研究 SACSIN 在该疾病病理学中的作用，但需要生成更可靠的人类细胞模型以更好地了解 ARSACS 的小脑病理生理学。人类诱导多能干细胞 (hiPSC) 的发现允许衍生出患者特异性细胞。这些细胞具有无限的自我更新能力和分化成不同神经细胞类型的能力，允许研究疾病机制、药物发现和细胞替代疗法。在这项研究中，我们讨论了 hiPSC 衍生的小脑类器官培养如何为靶向与 ARSACS 相关的致病突变提供新策略。我们还强调了这种 3D 细胞模型的优势和挑战，以及仍未解决的问题。