Antisense oligonucleotide therapy for Fukuyama type congenital muscular dystrophy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kobe University
• Principal Investigator: TANIGUCHI-IKEDA Mariko 神戸大学, 医学(系)研究科(研究院), 講師 (00410738)
• Co-Investigator(Renkei-kenkyūsha): KOBAYASHI Kazuhiro 神戸大学, 大学院医学研究科 分子脳科学, 准教授 (90324780)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 先天性筋ジストロフィー / 分子標的治療 / RNA創薬 / アンチセンス治療

Outline of Final Research Achievements

Fukuyama type congenital muscular dystrophy (FCMD) is a second common, severe childhood muscular dystrophy in Japan. All patients have ancestral insertion of a SINE-VNTR-Alu retrotransposal element (SVA) into a causative gene fukutin. We previously showed that aberrant mRNA splicing, induced by SVA exon-trapping caused FCMD.In this study, we optimized of the best, single AON for clinical trial. We re-designed AONs precisely around the splice sites and assessed the efficacy for exon trap inhibition of these AONs in FCMD patient cells and model mice. By testing on normal Fukutin production and functional analysis, we finally selected one best candidate AON termed AON-F. We also succeeded in improvement on production efficacy for AON-F. We show the promise of splicing modulation therapy as the first radical clinical treatment for FCMD in the near future.

Free Research Field

小児神経