Development of therapy for myotonic dystrophy by analyzing splicing mechanism using new splicing quantitative system

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H06161
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: YOSHIDA NATSUMI 東京大学, 生命科学ネットワーク, 特任助教 (10760069)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: myotonic dystrophy (DM) / chloride channel (CLCN1) / MBNL / CELF / antisenseoligonucleotide / Tat peptide

Outline of Final Research Achievements

Muscle hyper-excitability (myotonia) in patients with myotonic dystrophy is caused by the abnormality in alternative splicing of chloride channel (CLCN1). It is important for the treatment to normalize CLCN1 splicing. However, it was found that the genomic structures of mouse and human CLCN1 are considerably different, and we newly detected the abnormal splicing isoform exists in human CLCN1. So, it was necessary to quantify CLCN1 splicing by a new method using human CLCN1 genome. Therefore, we constructed a system to quantify only normal splicing, identify the sequence of antisense oligonucleotide that efficiently normalizes splicing of human CLCN1, and identify the splicing factor for the normalization. We expect that these results will be contributed to development of the treatment.

Free Research Field

分子細胞生物学、生化学、疾患生物学、核酸治療