Poster abstracts
Poster number 36 submitted by Allan Victor Cortes
Exon 10 skipping of ATXN3 as a potential therapy for Spinocerebellar Ataxia type 3 (SCA3)
Allan Victor Cortes (Biology, Lewis University), Ava Artz (Biology, Lewis University), Joseph Owens (Biology, Lewis University), Ana Botros (Biology, Lewis University), Aleksandra Borek (Biology, Lewis University)
Abstract:
Spinocerebellar Ataxia type 3 (SCA3), or Machado Joseph Disease, is an autosomal dominant disorder caused by excessive CAG repeats within exon 10 of the Ataxin-3 gene. As a result, the polyglutamine in the subsequent protein aggregates triggering neurodegeneration. Symptoms arise when CAG repeats exceed 44. Currently, there is no cure for the disease. Inducing exon 10 skipping using steric binging antisense oligonucleotides (ASO) removes the excessive repeats and leaves the binding domain and C-terminus intact. To determine the most efficient ASO chemistry, and sequence, and the therapeutic viability of skipping exon 10, C. elegans lacking endogenous ataxin gene, and patient fibroblasts were used. C. elegans were transfected with the human version of the ATXN3 containing 28 CAG repeats, 84 CAG repeats, or with exon 10 removed. Lifespan and locomotive functions were monitored. ASOs of various sequences, with 2’MOE modifications with and without phosphothioate modifications were tested in patient fibroblasts.
Keywords: SCA3, Spinocerebellar Ataxia, Machado Joseph