title: PTC124-mediated translational readthrough of a nonsense mutation causing Usher syndrome type 1C.
abstract: We investigated the therapeutic potential of the premature termination codon (PTC) readthrough-inducing drug PTC124 in treating the retinal phenotype of Usher syndrome, caused by a nonsense mutation in the USH1C gene. Applications in cell culture, organotypic retina cultures, and mice in vivo revealed significant readthrough and the recovery of protein function. In comparison with other readthrough drugs, namely the clinically approved readthrough-inducing aminoglycoside gentamicin, PTC124 exhibits significant better retinal biocompatibility. Its high readthrough efficiency in combination with excellent biocompatibility makes PTC124 a promising therapeutic agent for PTCs in USH1C, as well as other ocular and nonocular genetic diseases.
authors.affiliation: Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University Mainz, D-55099 Mainz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Goldmann
authors.forename: N
authors.initials: N
authors.lastname: Overlack
authors.forename: U
authors.initials: U
authors.lastname: Wolfrum
authors.forename: K
authors.initials: K
authors.lastname: Nagel-Wolfrum
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D018389:Codon, Nonsense / Q000187:drug effects*; D003598:Cytoskeletal Proteins; D018274:Electroporation; D005822:Genetic Vectors / Q000235:genetics; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D008164:Luminescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010069:Oxadiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D012160:Retina / Q000166:cytology / Q000473:pathology*; D052245:Usher Syndromes / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000097573:Red Fluorescent Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins; D005839:Gentamicins; D008164:Luminescent Proteins; D010069:Oxadiazoles; D000097573:Red Fluorescent Protein; C118970:USH1C protein, human; C515878:ataluren