Development of pH-responsive pharmacological chaperones for Gaucher disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K21167
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Metabolomics
• Research Institution: Tottori University
• Principal Investigator: NARITA Aya 鳥取大学, 医学部附属病院, 助教 (10569271)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: ライソゾーム病 / ゴーシェ病 / シャペロン療法

Outline of Final Research Achievements

Pharmacological chaperone therapy using the small molecule compound is promising therapy for neuropathic lysosomal storage diseases including Gaucher's disease.
We developed the pH-responsive pharmacological chaperones which is expected to obtain more high concentration of blood and cerebrospinal fluid.The chaperone effect of this compound showed a wider spectrum as compared with other chaperone compounds such as ambroxol. Also, combination of chaperone and exogenous enzyme showed synergic effect.
Additionally, secondary mitochondrial dysfunction was improved by the administration of this compound.

Free Research Field

神経変性疾患　ライソゾーム病

Academic Significance and Societal Importance of the Research Achievements

本化合物は幅広いスペクトラムのシャペロン効果を有するのみならず、酵素製剤との相乗作用や二次的なミトコンドリア機能の改善効果など、多様な作用を示すことから、現在治療法のないライソゾーム病の中枢神経に対する治療法として本化合物は有望である。