2022 Fiscal Year Final Research Report
Creation of therapeutic agent for Rett syndrome (CDKL5 deficiency disorder) using Kampo medicine
| Project/Area Number |
19K08264
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田中 輝幸 東京大学, 大学院医学系研究科(医学部), 准教授 (10246647)
片山 将一 立命館大学, 薬学部, 助教 (60779049)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | CDKL5 / 抑肝散 / 一味抜き成分 / 神経分化誘導作用 / Cdkl5ノックアウトマウス |
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| Outline of Final Research Achievements |
Yokukansan (YKS) is a Japanese traditional medicine called “Kampo medicine”. YKS consists of seven kinds of crude drugs: Atractylodes Lancea Rhizome, Poria Sclerotium, Cnidium Rhizome, Uncaria Hook, Japanese Angelica Root, Bupleurum Root and Glycyrrhiza. We were able to mix, extract, and dry a total of 7 types of extracts in YKS. We found that the extracts without Bupleurum Root and Glycyrrhiza reduced the efficiency of neuronal differentiation to about half. Finally, it was found that the neuronal differentiation-inducing action of YKS is at least partially mediated by glycyrrhizin and GSK3b signaling pathway.
Furthermore, we evaluated the effects of chronic treatment of YKS on Cdkl5 knockout (KO) mice. YKS administration for 3 months showed increased body weight, increased exploration in the brightly lit box in the light/dark transition test, and increased freezing in the fear conditioning test, suggesting modifying effects of YKS to the emotion and memory of Cdkl5 KO mice.
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| Free Research Field |
分子遺伝学、分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
レット症候群は、精神発達遅滞、てんかん等が有する稀少疾患でかつ現在に至るまで根本的な治療法が見出されていない難病である。本疾患（特にCDKL5欠失症）に対して、治療法やその候補薬を見出すことは社会的に意義深い。本研究で、日本古来の生薬である抑肝散が、細胞レベルで神経分化機能を促進し、また個体レベルでも情動と記憶機能に対する抑肝散の修飾効果を見出した。すなわち抑肝散は、CDKL5欠失症の症状改善のための治療薬の一つになりうる可能性があることを見出した。
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