Development of novel allosteric chaperone therapy for lysosomal storage diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Tottori University
• Principal Investigator: Higaki Katsumi 鳥取大学, 研究推進機構, 准教授 (90294321)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: シャペロン / アロステリック / ライソゾーム / 低分子化合物 / 治療法開発 / 中枢神経障害

Outline of Final Research Achievements

In this study, we explored the candidate chaperone compounds’ effects for beta-galactosidase deficiency and Gaucher disease in in vitro and cultured cell experiments. All the compounds showed no specific substrate competitive inhibition activity in vitro. And they showed enzyme enhancement activity in mutation specific manner in cultured cells. When cell treated with both chaperone and purified human normal beta-Glucosidase, synergetic effect was observed. In addition, chaperone for Gaucher disease showed restoration of mitochondrial abnormality in mutant GBA1 expressed cells. These results provided us important insights into efficacy of these compounds as candidate for chaperone therapy in the future.

Free Research Field

細胞遺伝学

Academic Significance and Societal Importance of the Research Achievements

遺伝性ライソゾーム病の脳病態に有効な治療法の開発が求められている現状に対し、薬理的シャペロン療法は有効な治療アプローチで、その開発研究は重要である。また、副反応の低い新しい治療法の開発は、将来的なシャペロン療法の応用のためも有用な知見を示すことができた。