Development of a PRIME editing therapy for Ataxia-8 due to the c.121 A to T point mutation
Ataxia UK
Laval University
Spastic ataxia-8 with hypo-myelinating leukodystrophy is an autosomal recessive progressive neurodegenerative disorder, which has been described by Chelban et al. in 2017. It is characterized by onset of primarily motor dysfunction within the first year of life. The patients initially have hypotonia and later develop ataxia, spasticity, and a pyramidal syndrome with weakness and loss of ambulation. Other symptoms include dystonia, dysarthria, and abnormal eye movements. Imaging of the brain shows cerebellar atrophy and hypo-myelinating leukodystrophy. In a subsequent publication in 2019, Chelban et al. described various point mutations in the NKX6-2 gene in eight families. This project will focus, as an example, on the correction by the PRIME editing technique of the c.121 A > T mutation. However, the other point mutations may also be eventually corrected by a similar PRIME editing approach.
2.1 Biological and endogenous factors