Establishing the genetic basis for tailor-made treatment of pediatric acquired demyelinating syndrome

• Project/Area Number: 18K07821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyushu University
• Principal Investigator: Ishizaki Yoshito 九州大学, 大学病院, 特別教員 (20572944)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 後天性脱髄症候群 / エキソーム解析 / iPS細胞 / ヒト多能性幹細胞 / 脳オルガノイド / ADS

Outline of Final Research Achievements

Acute encephalitis / encephalopathy in children often leaves serious sequelae in children who have been healthy until the onset, and has a great psychological and social impact not only on the affected children but also on their families. Epidemiological studies have been conducted, but the pathophysiology has not been elucidated, and no specific treatment has been developed. This study focuses on acquired demyelinating syndromes centered on acute disseminated encephalomyelitis, multiple sclerosis, and neuromyelitis optica, and combines clinical information with genetic information from exome analysis to optimize pediatric ADS. We created an information infrastructure for custom-made treatment and elucidated the pathophysiology using pluripotent stem cell-derived neurons and glial cells.

Academic Significance and Societal Importance of the Research Achievements

後天的な中枢神経系の炎症性脱髄を特徴とする神経疾患の総称であり、急性散在性脳脊髄炎、多発性硬化症、視神経脊髄炎を含む概念である。疫学調査の情報によると我が国の小児ADEMの推定罹患率は小児10万人当たり年間0.40人、小児MSの発症頻度は小児10万人当たり0.69人、NMOの発症頻度は小児10万人当たり0.06人であり、その発症には遺伝的因子が関与する。iPSCから神経細胞への分化し培養することができた。

Research Products

• [Journal Article] GNAO1 organizes the cytoskeletal remodeling and firing of developing neurons. (2020)
  • Author(s): Akamine S, Okuzono S, Yamamoto H, Setoyama D, Sagata N, Ohgidani M, Kato TA, Ishitani T, Kato H, Masuda K, Matsushita Y, Ono H, Ishizaki Y, Sanefuji M, Saitsu H, Matsumoto N, Kang D, Kanba S, Nakabeppu Y, Sakai Y, Ohga S.
  • Journal Title: FASEB J Volume: 34 Issue: 12 Pages: 16601-16621
  • DOI: 10.1096/fj.202001113r
  • Peer Reviewed / Open Access
• [Journal Article] De novo p.G696S mutation in COL4A1 causes intracranial calcification and late-onset cerebral hemorrhage: A case report and review of the literature. (2020)
  • Author(s): Kinoshita K, Ishizaki Y, Yamamoto H, Sonoda M, Yonemoto K, Kira R, Sanefuji M, Ueda A, Matsui H, Ando Y, Sakai Y, Ohga S.
  • Journal Title: Eur J Med Genet Volume: 63 Issue: 4 Pages: 103825-103825
  • DOI: 10.1016/j.ejmg.2019.103825
  • Peer Reviewed