Development a novel gene therapy for Lysosomal disease with neurological disorders

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09604
• 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, テクニカルスタッフ (00421206)
• Co-Investigator(Kenkyū-buntansha): 三宅 弘一 日本医科大学, 医学部, 准教授 (90267211)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 遺伝子治療 / 異染性白質ジストロフィー / アデノ随伴ウイルス / リソゾーム病 / 脳神経病変

Outline of Final Research Achievements

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficiency of arylsulfatase A (ASA) and characterized by neurological symptoms. To treat adult MLD mice, we generated self-complementary type 9 AAV vector expressing ASA (scAAV9/ASA), which could cross the BBB, and examined the feasibility of scAAV9/ASA mediated gene therapy for MLD. After scAAV9/ASA injection, immunohistochemical analysis showed efficient ASA expression was detected in systemic organs and brain. Alcian blue staining and quantative analysis of sulfatide showed decrease of the amount of stored sulfatide in scAAV9/ASA treated MLD mouse. In the behavior test, scAAV9/ASA treated mice showed a significant improvement in their ability to traverse narrow balance beams as compared to non-treated MLD mice. These data indicate that IV injection of scAAV9/ASA is effective for suppression of sulfatide storage in brain and this therapeutic approach may be useful for gene therapy of adult MLD patients.

Free Research Field

遺伝子治療

Academic Significance and Societal Importance of the Research Achievements

本研究では脳全体の広範な神経変性を伴う、異染性白質ジストロフィーをモデルとし、非侵襲的かつ安全で脳神経組織に長期の酵素補充療法が出来る治療法の開発を行った。
self-complementary AAV 9型を用いることで、脳組織の治療が可能になり、リソゾーム病のみならず、ALS、アルツハイマー病などの様々な脳神経病変を伴う疾患に応用が可能なると示唆された。