Attempt to improve multiple sclerosis progression by the control of intestinal mitochondrial oxidative stress

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15452
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Osaka University
• Principal Investigator: Shimizu Mikito 大阪大学, 医学系研究科, 招へい教員 (30817507)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 多発性硬化症 / 活性酸素種 / 酸化ストレス / ミトコンドリア / 食事療法

Outline of Final Research Achievements

At first, we revealed that oral administration of succinic acid, which is contained as food additives, increases the ratio of TH17 cells, which induce inflammation and promote demyelination, to regulatory T cells, which suppress inflammation, through IL-1β release from immune cells. And also we demonstrated that the release of IL-1β is associated with an increase of mitochondrial reactive oxygen species (mitoROS) in immune cells.
Now, we are investigating the immune system alteration in the central nervous system through succinate acid administration, using human astrocytes and mouse primary astrocytes as in vitro experiments. And in vivo, we are also planning an immune cell transfer experiment in order to clarify succinate acid effects to immune system.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

現在、多発性硬化症の治療薬は目覚しい進歩を遂げており、疾患コントロールはかなり改善されているが、重篤な副作用や、高額な医療費などまだまだ問題点も多い。またMRIの発達に症状が非常に軽微な時期から病変を検出することが可能となった一方、治療期間が延長する傾向にあることも、副作用や医療費の問題点を増大させている。今回提唱するような食事の工夫による免疫動態の制御が実現すれば、非常に安価で安全性の高い手段となるため、これらの現状を踏まえ必要性は増してくると思われる。