Development of innovative therapies for Rett syndrome with cell transplantation and functions control of microglia

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kurume University
• Principal Investigator: Takahashi Tomoyui 久留米大学, 医学部, 准教授 (20332687)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: レット症候群

Outline of Final Research Achievements

Rett Syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutation of MeCP2 (Methyl-CpG-binding protein 2) gene, which is a transcriptional regulator of the X chromosome. RTT occurs mainly in females and is characterized by intellectual disability, gait abnormalities, seizures, sleep problems, autonomic dysregulation, irregular breathing, and cardiac abnormalities, and it is eagerly desired to elucidate the pathogenic mechanism and develop a therapeutic method.
We analyzed the involvement of microglia in RTT pathology using the RTT model (MeCP2-null) ES cells and mice. As a result, gene expression was changed in MeCP2-deficient microglia and differentiation-induced microglia-like cells compared with wild-type cells, but no obvious abnormality in physiological function was observed. However, MeCP2 deficiency affects the immune system in the whole body, and we continue to analyze the factors that control the immune system, including microglia.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

近年、様々な精神疾患の病態メカニズムにおける炎症の関与が示されており、脳内の免疫を司るミクログリアの役割は注目されている。最近、神経発達症の一つとして知られるRTTにおいても、病態における免疫系の関与が示唆されている。このことから、RTT病態におけるミクログリアの働きに関する本研究は、神経精神疾患と炎症との関係を明らかにする一助になると考えられ、基礎医学的に有意義なものと考えられる。