Fogel Brent L, Klopstock Thomas, Lynch David R, Maltecca Francesca, Verma Mayank, Minassian Berge A, Platt Frances M, Gonçalves Débora Farina, Puccio Hélène, Roos Andreas, Synofzik Matthis
Departments of Neurology and Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Department of Neurology with Friedrich-Baur-Institute, University Hospital of Ludwig-Maximilians-Universität München, Munich, Germany.
Ann Neurol. 2025 Sep;98(3):448-470. doi: 10.1002/ana.27271. Epub 2025 Jun 4.
Autosomal recessive cerebellar ataxias (ARCAs) represent over 200 clinically heterogeneous genetic conditions involving degeneration of the cerebellum and associated tracts with resultant impairment of balance and coordination. Advancements in genomic testing have enabled rapid identification of the majority of known recessive disorders, shifting research focus to the development of targeted mechanistic treatments addressing underlying physiological pathways. Molecular classification allows recognition of cellular, biochemical, and genetic targets for high-effect precision therapy development. ARCAs represent a significant global health burden, requiring establishment of a robust pathway for novel therapeutic discovery through modification of mechanisms of disease pathogenesis and subsequent clinical trial development. ANN NEUROL 2025;98:448-470.
常染色体隐性遗传性小脑共济失调（ARCAs）代表200多种临床异质性遗传疾病，涉及小脑及其相关神经束的退化，进而导致平衡和协调能力受损。基因组检测技术的进步使得大多数已知隐性疾病能够快速得到诊断，研究重点也因此转向针对潜在生理途径开发靶向性机制治疗方法。分子分类有助于识别用于高效精准治疗开发的细胞、生化和遗传靶点。ARCAs是一项重大的全球健康负担，需要建立一个强大的途径，通过改变疾病发病机制来发现新的治疗方法，并随后开展临床试验。《神经病学年鉴》2025年；98:448 - 470。
