Development of novel gene therapy for CNS disorders of lysosomal diseases

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591529
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nippon Medical School
• Principal Investigator: MIYAKE NORIKO 日本医科大学, 医学部, その他 (00421206)
• Co-Investigator(Kenkyū-buntansha): MIYAKE Koichi 日本医科大学, 医学部, 准教授 (90267211)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 異染性白質ジストロフィー / 遺伝子治療 / アデノ随伴ウイルス / 中枢神経病変

Outline of Final Research Achievements

We examined the feasibility of adeno-associated viral serotype-9 (AAV9)-mediated systemic neonatal gene therapy of metachromatic leukodystrophy (MLD) mice to treat central nervous system (CNS) disorders. AAV9 vector expressing human arylsulfatase A (AAV9/ASA) was injected into the jugular vein of newborn MLD mice. Global gene transfer into the brain, across the blood brain barrier, and long-term ASA expression in the CNS were detected in treated mice. Significant inhibition of the accumulation of sulfatide (Sulf) in the brain was confirmed by Alcian blue staining and biochemical analysis of the Sulf content. In a behavior test, treated mice showed a greater ability to traverse narrow balance beams than untreated mice. These data clearly demonstrate that MLD mice can be effectively treated through neonatal systemic injection of AAV9/ASA. Thus, AAV9 mediated systemic neonatal gene therapy is useful to treat various CNS disorders.

Free Research Field

医歯薬学