Drug Development for GM1 Gangliosidosis using the patients-derived iPS cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19654
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kumamoto University
• Principal Investigator: Kajihara Ryutaro 熊本大学, 大学院生命科学研究部(保), 助教 (00738221)
• Research Collaborator: ERA Takumi 熊本大学, 発生医学研究所, 教授 (00273706) ; NUMAKAWA Tadahiro 熊本大学, 発生医学研究所, 特定事業研究員 (40425690) ; ENDO Fumio 熊本大学, 大学院生命科学研究部, 教授 (00176801) ; MASTUMOTO Shirou 熊本大学, 医学部附属病院, 講師 (70467992)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: GM1ガングリオシドーシス

Outline of Final Research Achievements

GM1 gangliosidosis is a type of lysosomal storage disease, which is caused by lack of lysosomal β-galactosidase activity, leading to progressive neurodegeneration due to massive accumulation of GM1 ganglioside in the brain. Here, we generated the GM1 gangliosidosis-derived iPSCs to elucidate the pathological mechanisms of neural dysfunction under the disease and to find new drug candidates. Neurons from the patients-derived iPSCs exhibited the GM1 ganglioside accumulation and impaired pre-synaptic function. High throughput drug screening system using the patient-derived neural cells found two compounds as novel drug candidates. These could significantly reduce GM1 ganglioside accumulation in vitro and in vivo, and restored the presynaptic dysfunction in the patient-derived neurons. Our findings demonstrated the potential value of the patients-derived iPSC lines for the cellular model of GM1 gangliosidosis and that two compounds are the potential candidates as drugs in the future.

Free Research Field

細胞生物学