Development to Neiman pick C type disease treatment of Mal-cyclodextrin

2016 Fiscal Year Final Research Report

• Project/Area Number: 26505012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: オミクス計測科学
• Research Institution: Mukogawa Women's University
• Principal Investigator: Okada Yasuyo 武庫川女子大学, 薬学部, 講師 (70211117)
• Co-Investigator(Renkei-kenkyūsha): BAMBA takeshi 九州大学, 生体防御医学研究所, 教授 (10432444)
• Research Collaborator: UEDA erika
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ニーマンピックＣ型病 / マルトシル－βシクロデキストリン / コレステロール / リソゾーム / LC/MS

Outline of Final Research Achievements

Niemann-Pick Type C (NPC) disease is a lysosomal storage disease characterized by excess accumulation of unesterified cholesterol in the lysosomes. β-cyclodextrin derivatives (βCDs) form inclusion complexes with unesterified cholesterol and are a subject of intense research in the context of treating the NPC disease. In this study, we used quantitative LC/MS/MS to demonstrate that a 6-O-α-maltosyl-β-cyclodextrin derivative (Mal-βCD) is internalized by Npc1 KO and CHO-JP17 cells by fluid-phase endocytosis. This is followed by Mal-βCD transport to the lysosomes, where the majority of Mal-βCD is metabolized to Glc-βCD. Finally, the lysosomal βCDs and unesterified cholesterol are released to the extracellular fluid. We believe that our study makes a significant contribution to the literature because it not only provides insight into the intracellular fate of internalized Mal-βCD but also may inform future treatment of the NPC disease.

Free Research Field

薬学