PMC:5985359 / 36256-37091 JSONTXT

{"project":"2_test","denotations":[{"id":"29526280-28405024-2044802","span":{"begin":144,"end":146},"obj":"28405024"},{"id":"29526280-28641106-2044803","span":{"begin":148,"end":150},"obj":"28641106"},{"id":"29526280-27112497-2044804","span":{"begin":152,"end":154},"obj":"27112497"},{"id":"29526280-22859208-2044805","span":{"begin":156,"end":158},"obj":"22859208"},{"id":"29526280-22726834-2044806","span":{"begin":160,"end":162},"obj":"22726834"}],"text":"ASOs have recently emerged as a powerful therapeutic option for disease intervention, including those caused by trinucleotide repeat expansions.10, 39, 40, 41, 42 Here we show that a non-coding CTG trinucleotide repeat expansion in TCF4 (CTG18.1) confers greater than 76-fold risk for FECD in a large white British and Czech cohort. We demonstrate that primary CECs derived from FECD-affected subjects display the predicted hallmarks of primary and downstream repeat-expansion-associated pathology, and subsequently show that these changes are reversed by an ASO treatment specifically targeted at the CTG18.1 trinucleotide repeat expansion. An ASO-based treatment could therefore offer an innovative therapeutic approach that could benefit a substantial number of individuals affected by this common and sight-threatening condition.43"}