Spinocerebellar Ataxia

The spinocerebellar ataxias (SCAs) are a large group of autosomal dominant neurodegenerative disorders characterized by progressive cerebellar dysfunction. The most common mechanism involves polyglutamine (polyQ) repeat expansions in specific genes, leading to toxic protein accumulation and neuronal death. SCA1, SCA2, SCA3 (Machado-Joseph disease), SCA6, and SCA7 are polyQ expansion disorders and account for the majority of cases. The cerebellum is the primary target, but many SCA subtypes also affect the brainstem, spinal cord, peripheral nerves, and basal ganglia. Cerebellar Purkinje cells are particularly vulnerable, and their progressive loss underlies the characteristic gait and limb ataxia. As the disease advances, patients develop dysarthria, dysphagia, and oculomotor abnormalities. Most SCA subtypes progress over 10-30 years, with patients eventually requiring wheelchair assistance and full-time care. Currently there is no approved disease-modifying treatment, though troriluzole (a glutamate modulator) was studied in a major clinical program showing slowed disease progression.