Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies.
Fogel BL., Klopstock T., Lynch DR., Maltecca F., Verma M., Minassian BA., Platt FM., Gonçalves DF., Puccio H., Roos A., Synofzik M.
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.