Translational research on the effects of intracerebroventricular administration of 2-hydroxypropyl-beta-cyclodextrin against Niemann-Pick disease type C

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: Irie Tetsumi 熊本大学, 大学院生命科学研究部(薬), 教授 (60150546)
• Co-Investigator(Renkei-kenkyūsha): ERA Takumi 熊本大学, 発生医学研究所, 教授 (00273706) ; ISHITSUKA Yoichi 熊本大学, 生命科学研究部, 准教授 (70423655) ; KONDO Yuki 熊本大学, 生命科学研究部, 助教 (90721879) ; OKADA Yasuyo 武庫川女子大学, 薬学部, 講師 (70211117)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: niemann-pick病C型 / cyclodextrin / 脳室内投与療法

Outline of Final Research Achievements

This translational research was conducted to evaluate the effects of intracerebroventricular administration of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) against Niemann-Pick disease type C models and patients. Although a pre-symptomatic injection of HPBCD showed more potent effects on the lifespan and Purkinje cell loss in NPC model mice, a post-symptomatic HPBCD also significantly attenuated the disease states compared with control group. We proved that HPBCD had an optimal concentration range to exert attenuating effects against NPC manifestation in model cells. In additon, physical and chemical properties, such as degrees of substitution of the hydroxypropyl group, also were assessed. Furthermore, we also perfomed pharmacokinetic analysis in NPC patients treated with HPBCD. The results of this study will provide a rationale for the optimization of intracerebroventricular HPBCD therapy for NPC.

Free Research Field

医療薬学