Exon 45 skipping theraphy using iPS cells deleted exons 46-55 in the DMD gene

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04756
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Shinshu University
• Principal Investigator: Akinori Nakamura 信州大学, 医学部, 特任教授 (10303471)
• Co-Investigator(Kenkyū-buntansha): 柴 祐司 信州大学, 学術研究院医学系, 教授 (70613503) ; 宮崎 大吾 信州大学, 医学部附属病院, 講師(特定雇用) (80596370) ; 武田 伸一 国立研究開発法人国立精神・神経医療研究センター, 神経研究所, 所長 (90171644)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ジストロフィン / エクソン・スキップ治療 / アンチセンスオリゴヌクレオチド / iPS細胞 / 心筋細胞 / 網羅的遺伝子発現解析

Outline of Final Research Achievements

A deletion of exons 45-55 in the DMD gene is associated with mild skeletal muscle involvement. Many DMD patients having a mutation within exons 45-55 region could be treated if we were able to skip the entire exon 45-55 region. We established iPS cell lines from T lymphocytes donated from DMD patient with a deletion of exon 46-55, and differentiated iPS cells toward cardiomyocytes. The cardiomyocytes supplemented with phosphorodiamidate morpholono oligomers (PMO) to skip exon 45. The efficiency of exon 45 skipping was occurred with dose-dependent manner. We confirmed a recovery of short length dystrophin proteins. The microarray showed there was no significant difference in the profiling of gene expression between before and after the therapy. The exon skipping therapy using PMO was little affecting other gene expression, and it was possible for exon skipping therapy safely.

Free Research Field

神経内科学