Therapeutic efficacy of antisense oligonucleotides in mouse models of CLN3 Batten disease.

ABSTRACT: CLN3 Batten disease is an autosomal recessive, neurodegenerative, lysosomal storage disease caused by mutations in CLN3, which encodes a lysosomal membrane protein^1-3. There are no disease-modifying treatments for this disease that affects up to 1 in 25,000 births, has an onset of symptoms in early childhood and typically is fatal by 20-30 years of life^4-7. Most patients with CLN3 Batten have a deletion encompassing exons 7 and 8 (CLN3^∆ex7/8), creating a reading frameshift^7,8. Here we demonstrate that mice with this deletion can be effectively treated using an antisense oligonucleotide (ASO) that induces exon skipping to restore the open reading frame. A single treatment of neonatal mice with an exon 5-targeted ASO-induced robust exon skipping fo

SUBMITTER: Centa JL 

PROVIDER: S-EPMC8008709 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature