| RRC ID |
58085
|
| 著者 |
Sato M, Shiba N, Miyazaki D, Shiba Y, Echigoya Y, Yokota T, Takizawa H, Aoki Y, Takeda S, Nakamura A.
|
| タイトル |
Amelioration of intracellular Ca2+ regulation by exon-45 skipping in Duchenne muscular dystrophy-induced pluripotent stem cell-derived cardiomyocytes.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Duchenne muscular dystrophy (DMD) is a devastating muscle disorder caused by frameshift mutations in the DMD gene. DMD involves cardiac muscle, and the presence of ventricular arrhythmias or congestive failure is critical for prognosis. Several novel therapeutic approaches are being evaluated in ongoing clinical trials. Among them, exon-skipping therapy to correct frameshift mutations with antisense oligonucleotides is promising; however, their therapeutic efficacies on cardiac muscle in vivo remain unknown. In this study, we established induced-pluripotent stem cells (iPSCs) from T cells from a DMD patient carrying a DMD-exon 46-55 deletion, differentiated the iPSCs into cardiomyocytes, and treated them with phosphorodiamidate morpholino oligomers. The efficiency of exon-45 skipping increased in a dose-dependent manner and enabled restoration of the DMD gene product, dystrophin. Further, Ca2+-imaging analysis showed a decreased number of arrhythmic cells and improved transient Ca2+ signaling after exon skipping. Thus, exon-45 skipping may be effective for cardiac involvement in DMD patients harboring the DMD-exon 46-55 deletion.
|
| 巻・号 |
520(1)
|
| ページ |
179-185
|
| 公開日 |
2019-11-26
|
| DOI |
10.1016/j.bbrc.2019.09.095
|
| PII |
S0006-291X(19)31825-X
|
| PMID |
31585729
|
| MeSH |
Arrhythmias, Cardiac / metabolism
Calcium / metabolism*
Cell Culture Techniques
Cell Differentiation
Cell Nucleus / metabolism
Dystrophin / genetics
Exons
Female
Gene Deletion
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism
Japan
Muscular Dystrophy, Duchenne / genetics*
Muscular Dystrophy, Duchenne / metabolism*
Myocytes, Cardiac / metabolism*
Young Adult
|
| IF |
2.985
|
| 引用数 |
2
|
| リソース情報 |
| ヒト・動物細胞 |
253G1(HPS0002) |
