CAG Repeat Length Tied to Progression in Common Spinocerebellar Ataxias

In a study presented at MDS 2021, researchers assessed the progression of spinocerebellar ataxias type 1, 2, 3, and 6, an autosomal dominantly inheritance, to identify factors that influence the transition to higher disability.

Among patients with spinocerebellar ataxias (SCA) type 1, 2, and 3, an autosomal dominantly inheritance, CAG length size was associated with faster disease progression, and had a similar effect in female patients with SCA6, according to study results presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) Virtual Congress 2021, held from September 17 to 22, 2021.

Previous studies have evaluated progression rates of the disorders with the Scale for the Assessment and Rating of Ataxia (SARA) and other assessment measures for long-term follow-up periods, but there is limited research that covers the whole duration of the disease, according to the researchers. The current study observed the evolution of disability in this patient population using a staging system to identify factors that influence the transition to increased disability.

Researchers analyzed the longitudinal data of 677 RISCA and EUROSCA cohort participants’ 3138 visits. They categorized the disability into stages: stage 0 (no gait difficulties), stage 1 (gait difficulties), stage 2 (permanent reliance on a walking aid), and stage 3 (confinement to wheelchair). To describe transitions between stages and estimate duration in each stage for each genotype, the researchers used a multistate model with proportional transition hazards. They examined how sex and CAG repeat length influenced progression.

Across the disorders, mean SARA scores ranged from 1.9 to 2.6 in stage 0, 10.8 to 12.8 in stage 1, 19.8 to 24.8 in stage 2, and 29.7 to 34.3 in stage 4. In patients with SCA1, 2 and 3, CAG repeat length was linked to faster progression ((hazard ratio (HR)): 1.11, 95% confidence interval (CI): 1.062-1.164), SCA2 (1.16, 1.075-1.245), and SCA3 (1.08; 1.016-1.156)). Among patients with SCA6, females were more likely to experience faster progression (HR: 1.67, 95% CI: 1.077-2.577).

“Our study provides a comprehensive view of disease evolution in SCA1, 2, 3, and 6 based on the prospective assessment of disability stages which are of immediate relevance for affected individuals,” the researchers concluded. “Our data are important for counselling of patients, assessment of the relevance of outcome markers, and design of clinical trials.”


Jacobi H, Schaprian T, Beyersmann J, et al. Evolution of disability in spinocerebellar ataxias type 1, 2, 3, and 6. Presented at: MDS Virtual Congress 2021; September 17-22, 2021. Abstract 34.