Stem cell replacement therapy as a potential treatment for SCA1 disease

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by expansion of CAG trinucleotide repeats in the ataxin-1 gene and is characterized by cerebellar ataxia and progressive motor deterioration. The ataxin-1 protein is involved in transcription and RNA processing. SCA1 pathogenesis appears to be related to a gain-of-function effect that is caused by toxic mutant ataxin-1-derived aggregates or cellular dysfunction through an abnormal interaction between mutated and normal proteins. Recent studies have clarified the molecular mechanisms of SCA1 pathogenesis, which provide direction for future treatments. Therapeutic hope has come from observations including the reduction of aggregates and alleviation of the pathogenic phenotype by the application of potent inhibitors and RNA interference. However, no treatment is currently available for SCA1 disease. In this chapter, we discuss the potential of stem cells as a therapeutic approach to SCA1.