CRISPR-based gene therapy for spinocerebellar ataxia type 3

CRISPR-based gene therapy for spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is an investigational genetic treatment that uses the CRISPR/Cas9 genome editing system to target and modify the mutant ATXN3 gene responsible for SCA3. The mechanism of action involves using guide RNAs to direct Cas9 nuclease to the expanded CAG repeat region in exon 10 of ATXN3, enabling precise excision or correction of pathogenic polyglutamine expansions. This approach aims to reduce or eliminate production of toxic mutant ataxin-3 protein while preserving normal protein function. Preclinical studies have demonstrated successful deletion or correction of the expanded polyQ region in patient-derived induced pluripotent stem cells and animal models, with restoration of cellular function and potential reversal of disease phenotypes[1][2][5]. The primary indication is Spinocerebellar Ataxia Type 3.

Other names

CRISPR/Cas9-mediated gene editing for SCA3CRISPR/Cas9-based therapy for Machado-Joseph disease