Investigation of inflammatory factors affecting the efficacy of the molecular therapies for muscular dystrophy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hyogo Medical University
• Principal Investigator: Yasuhiro Takeshima 兵庫医科大学, 医学部, 教授 (40281141)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 筋ジストロフィー / 分子治療 / 炎症性物質 / エクソンスキッピング / アンチセンスオリゴヌクレオチド

Outline of Final Research Achievements

To enhance the efficacy of antisense oligonucleotide (AS-oligo)-mediated exon skipping therapy for Duchenne muscular dystrophy (DMD), the difference of the efficacy of the same AS-oligo among DMD cases and the involvement of inflammatory factors to exon skipping therapy were examined. At the beginning the efficacy of the AS-oligo inducing the skipping of exon 45 (AO85) was examined using cultured muscle cells of several DMD patients. In each case, exon 45 skipping was induced by AO85, as expected; however, the skipping efficacy was different from patient to patient. Furthermore, administration of AO85 to DMD cases resulted in the change of some serum inflammatory factors. These results suggested that exon skipping efficacy is modulated by some cis-element, and some inflammation factors may affect the efficacy of AS-oligo therapy.

Free Research Field

小児科学