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- W2958687511 abstract "Myotonic dystrophy type 1 (DM1) is a multi-systemic disease that presents with clinical symptoms including myotonia, cardiac dysfunction and cognitive impairment. DM1 is caused by a CTG expansion in the 3' UTR of the DMPK gene. The transcribed expanded CUG repeat RNA sequester the muscleblind-like (MBNL) and up-regulate the CUG-BP Elav-like (CELF) families of RNA-binding proteins leading to global mis-regulation of RNA processing and altered gene expression. Currently, there are no disease-targeting treatments for DM1. Given the multi-step pathogenic mechanism, combination therapies targeting different aspects of the disease mechanism may be a viable therapeutic approach. Here, as proof-of-concept, we studied a combination of two previously characterized small molecules, erythromycin and furamidine, in two DM1 models. In DM1 patient-derived myotubes, rescue of mis-splicing was observed with little to no cell toxicity. In a DM1 mouse model, a combination of erythromycin and the prodrug of furamidine (pafuramidine), administered orally, displayed both additive and synergistic mis-splicing rescue. Gene expression was only modestly affected and over 40 % of the genes showing significant expression changes were rescued back toward WT expression levels. Further, the combination treatment partially rescued the myotonia phenotype in the DM1 mouse. This combination treatment showed a high degree of mis-splicing rescue coupled with low off-target gene expression changes. These results indicate that combination therapies are a promising therapeutic approach for DM1." @default.
- W2958687511 created "2019-07-23" @default.
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- W2958687511 date "2019-07-17" @default.
- W2958687511 modified "2023-10-16" @default.
- W2958687511 title "Combination Treatment of Erythromycin and Furamidine Provides Additive and Synergistic Rescue of Mis-splicing in Myotonic Dystrophy Type 1 Models" @default.
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- W2958687511 cites W2004901342 @default.
- W2958687511 cites W2008929289 @default.
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- W2958687511 doi "https://doi.org/10.1021/acsptsci.9b00020" @default.
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- W2958687511 hasPublicationYear "2019" @default.
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