Modelling Duchenne muscular dystrophy in MYOD1-converted urine-derived cells treated with 3-deazaneplanocin A hydrochloride.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Adenosine/*analogs & derivatives ; Mesenchymal Stem Cells/*metabolism ; Muscular Dystrophy, Duchenne/*genetics ; MyoD Protein/*genetics; Adenosine/administration & dosage ; Adolescent ; Adult ; Child ; Exons ; Humans ; Male ; Mesenchymal Stem Cells/drug effects ; Models, Biological ; Muscular Dystrophy, Duchenne/pathology ; MyoD Protein/metabolism ; Oligonucleotides, Antisense/therapeutic use

Duchenne muscular dystrophy (DMD) is a severe muscle disorder characterised by mutations in the DMD gene. Recently, we have completed a phase I study in Japan based on systemic administration of the morpholino antisense that is amenable to exon-53 skipping, successfully. However, to achieve the effective treatment of DMD, in vitro assays on patient muscle cells to screen drugs and patient eligibility before clinical trials are indispensable. Here, we report a novel MYOD1-converted, urine-derived cells (UDCs) as a novel DMD muscle cell model. We discovered that 3-deazaneplanocin A hydrochloride, a histone methyltransferase inhibitor, could significantly promote MYOGENIN expression and myotube differentiation. We also demonstrated that our system, based on UDCs from DMD patients, could be used successfully to evaluate exon-skipping drugs targeting DMD exons including 44, 50, 51, and 55. This new autologous UDC-based disease modelling could lead to the application of precision medicine for various muscle diseases.

Erratum in: Sci Rep. 2020 Feb 7;10(1):2462. (PMID: 32034287)

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0 (MyoD Protein)
0 (MyoD1 myogenic differentiation protein)
0 (Oligonucleotides, Antisense)
544SH4020S (3-deazaneplanocin)
K72T3FS567 (Adenosine)

Date Created: 20190309 Date Completed: 20200929 Latest Revision: 20200929

20231215

PMC6405839

10.1038/s41598-019-40421-z

30846748