PMC:5985359 / 43296-44416 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5985359","sourcedb":"PMC","sourceid":"5985359","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5985359","text":"In summary, we demonstrate proof-of-concept data that a targeted (CAG)7 ASO treatment reduces gain-of-function RNA toxicity induced by TCF4 CTG18.1 expansion, in a cellular and human genomic context. With the absence of FECD animal models, human ex vivo models are vital, both to provide a validation of the therapeutic approach for FECD and to continue the translation of ASO therapies into the clinic. ASO therapies are already in clinical trials for a variety of repeat expansion disorders including DM141 and Huntington disease (MIM: 143100), and additionally, intraocular ASO therapies are proposed for retinitis pigmentosa (RP [MIM: 268000]), RP associated with Usher syndrome (MIM: 608400), and Leber congenital amaurosis (MIM: 610142).49, 50, 51, 52 We propose that our proof-of-concept study provides evidence to translate this therapeutic approach to FECD given the accessibility of the diseased tissue and the relatively delayed onset of disease, which provides a window of opportunity to identify at risk individuals with TCF4 repeat expansions and prevent disease progression in pre-symptomatic individuals.","tracks":[{"project":"2_test","denotations":[{"id":"29526280-22859208-2044816","span":{"begin":505,"end":508},"obj":"22859208"},{"id":"29526280-26436889-2044817","span":{"begin":743,"end":745},"obj":"26436889"},{"id":"29526280-23380860-2044818","span":{"begin":747,"end":749},"obj":"23380860"},{"id":"29526280-27106101-2044819","span":{"begin":751,"end":753},"obj":"27106101"},{"id":"29526280-27151457-2044820","span":{"begin":755,"end":757},"obj":"27151457"}],"attributes":[{"subj":"29526280-22859208-2044816","pred":"source","obj":"2_test"},{"subj":"29526280-26436889-2044817","pred":"source","obj":"2_test"},{"subj":"29526280-23380860-2044818","pred":"source","obj":"2_test"},{"subj":"29526280-27106101-2044819","pred":"source","obj":"2_test"},{"subj":"29526280-27151457-2044820","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#9397ec","default":true}]}]}}