2020/12/21
Keio University School of Medicine
In a joint research project, Lecturer Tomohiko Akiyama and Professor Minoru Ko of The Sakaguchi Laboratory (System Medicine) at the Keio University School of Medicine, and Principal Researcher Hidehisa Iwata of the Neuroscience Drug Discovery Unit at Takeda Pharmaceutical Company Limited, have successfully achieved early detection of Parkinson's disease-inducing factors using a technology that rapidly produces highly pure neurons from iPS cells.
The aggregation of alpha-synuclein in neurons is deeply involved in the onset of Parkinson's disease, but the underlying cause is not well understood. Since patients with Gaucher's disease, a congenital metabolic disorder, have a high incidence of Parkinson's disease, it is thought that abnormalities in the metabolic system, particularly the accumulation of glycolipids, are one of the causes of synuclein abnormalities.
While the use of disease-specific iPS cells is an effective approach to elucidating these pathologies, there has been a time constraint, as the production of neurons typically takes more than a month. In this study, we rapidly produced neurons from iPS cells derived from Gaucher's disease patients using a synthetic mRNA differentiation induction method that can produce neurons in one week. As a result, we succeeded in detecting phenotypes related to Parkinson's disease, such as the accumulation of glycolipids and the phosphorylation of alpha-synuclein, at just 10 days after the start of differentiation. Furthermore, by inhibiting the accumulation of glycolipids, we were able to suppress the phosphorylation of alpha-synuclein, thereby elucidating part of the pathological mechanism.
With conventional differentiation induction methods, it takes more than two months to detect phenotypes. Therefore, these findings are expected to be applied to drug discovery and development, where accelerated speed is required.
The results of this research were published online in the American scientific journal "STEM CELLS Translational Medicine" on December 20, 2020 (US Eastern Time).
Please see below for the full press release.