Research on Fukuyama musucular dystrophy towards clincal trial using antisense oligonucleotids

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09621
• 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 (谷口) 神戸大学, 医学研究科, 特命准教授 (00410738)
• Co-Investigator(Renkei-kenkyūsha): KEIKO Ishigaki 東京女子医科大学, 医学部 医学科, 講師 (10366304)
• Research Collaborator: HARADA Risa 神戸大学, 大学院医学研究科, 医員 (30736864) ; YOSHIDA Masaru 神戸大学, 大学院医学研究科, 准教授 (00419475) ; TAKAO Keizo 富山大学, 医学研究科, 教授 (80420397) ; NEGISHI Youichi 東京薬科大学, 准教授 (50286978)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: スプライシング異常 / 筋ジストロフィー / RNA創薬

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 show that aberrant mRNA splicing, induced by SVA exon-trapping caused FCMD (Taniguchi-Ikeda M et al, Nature 2011). Introduction of three cocktailed antisense oligonucleotides (AONs) targeting around these splice sites prevented pathogenic splicing in FCMD patient cells and model mice, and normalized protein production and functions of Fukutin as well as O-glycosylation of α-dystroglycan. Here we show the results of an optimization of the best, single AON for clinical trial. We tested if these AONs are effective in Central Nervous System (CNS). We could successfully deliver AONs to CNS in model mice.

Free Research Field

神経・筋疾患