Poster abstracts
Poster number 123 submitted by Ezra Samson
ATXN3 exon 10 skipping as a potential therapeutic for SCA3
Allan Victor Cortes (Lewis Biology Department), Ava Artz (Lewis Biology Department), Joseph Owens (Lewis Biology Department), Ezra Samson (Lewis Biology Department)
Abstract:
SCA3 (Machado Joseph Disease) is a neurodegenerative disease caused by excessive glutamine, CAG, repeats in the Ataxin-3 protein. A healthy individual can have as many as 44 CAG repeats, while symptoms of the disease start appearing from 45 CAG repeats and higher. The polyglutamine causes the protein to aggregate and leads to neuronal death. The symptoms of SCA3 range from impaired motor functions to death. Currently, there is no cure for the disease. Skipping of exon 10 of Ataxin-3 removed the CAG repeat but leaves the binding domain and C-terminus of the protein intact. To determine if this is a viable therapeutic method in a whole organism, and determine ASO’s with a unique backbone chemistry would be more efficient than traditional chemistries, C. elegans with the endogenous Ataxin-3 gene knocked out, their wildtype counterparts, and human fibroblasts were used. Lifespan and movement data was assessed over a 12-day period in C. elegans. The functionality of the ASO backbone modifications to induce exon 10 skipping were also assessed.
Keywords: SCA3