Investigation of immune tolerance induction method for gene therapy of muscular dystrophy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nippon Medical School
• Principal Investigator: Hayashita-Kinoh Hiromi (早下裕美) 日本医科大学, 医学部, 助教 (60532728)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 遺伝子治療 / 筋ジストロフィー / 免疫応答 / 間葉系幹細胞 / 疾患モデル

Outline of Final Research Achievements

Duchenne muscular dystrophy (DMD) is a severe congenital disease due to mutations in the dystrophin gene. Supplementation of dystrophin using rAAV has promise as a treatment of DMD, however, host immune responses against the vector as well as transgene products have been denoted in the clinical studies. Here, we transduced rAAV9-microdystrophin(uDys) with MSCs to DMD dog to investigate the therapeutic effects of an rAAV-uDys under conditions of immune tolerance. MSCs and rAAV9-Luc/rAAV9-uDys were intravenously injected into the normal or CXMDJ dog at 8 weeks old. Seven days after injection, MSCs were systemically injected again. At 8 days after 1st injection, rAAV9-Luc/rAAV9-uDys was intramuscularly or intravenously injected into the same dog. Administration of rAAV following MSCs treatment resulted in higher expression of transgene, compared to the rAAV transduction alone. The CXMDJ treated with MSCs and rAAV9-uDys showed functional improvement than other DMD dogs of same age.

Free Research Field

生化学