ATXN3 exon 10 splice-switching ASO

Cure Rare Disease is developing a splice-switching antisense oligonucleotide (ASO) for the treatment of Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph disease. The therapy targets exon 10 of the ATXN3 pre-mRNA, which contains the pathogenic expanded CAG repeat mutations responsible for the disease. By utilizing steric blocking to induce exon skipping, the ASO prevents the inclusion of exon 10 in the final mRNA transcript. This results in the production of a slightly shorter ataxin-3 protein that lacks the toxic polyglutamine expansion but retains its essential functional domains. The program has demonstrated functional improvements in preclinical mouse models and is currently in the IND-enabling stage of development, supported by a $5.69 million grant from the California Institute for Regenerative Medicine (CIRM) and having received FDA Orphan Drug Designation in May 2025.

Other names

Cure Rare Disease SCA3 programATXN3 ASOATXN-3 ASOATXN 3 ASOMachado-Joseph disease ASO