Novel therapy for spinal cord damage of neuromyelitis optica via regulation of BK channel

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07869
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Kyushu University
• Principal Investigator: Matsushita Takuya 九州大学, 大学病院, 講師 (00533001)
• Co-Investigator(Kenkyū-buntansha): 渡邉 充 九州大学, 大学病院, 助教 (30748009) ; 吉良 潤一 国際医療福祉大学, 福岡薬学部, 教授 (40183305) ; 磯部 紀子 九州大学, 医学研究院, 教授 (60452752) ; 真崎 勝久 九州大学, 大学病院, 講師 (90612903)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 視神経脊髄炎スペクトラム障害 / アストロサイト / KCNMA1

Outline of Final Research Achievements

We investigated associations between KCNMA1, a component of BK channel, and spinal cord damage in patients with neuromyelitis optic spectrum disorders (NMOSD). Immunoreactivity in the perivascular area of the central gray matter, where aquaporin-4 (AQP4), an antigen targeted by specific autoantibodies in NMOSD, is observed. Primary astrocyte cultures exhibited KCNMA1 expression in the membrane similar to AQP4, as well as in the perikaryon. These astrocytes were damaged to death by addition of IgG purified from serum of a NMOSD patient with anti-AQP4 antibody and complements. Addition of modulator of KCNMA1, ISO or PAX , did not elicit any effects on IgG-complement-mediated damage .However, NMO-IgG addition to the cells induced translocation of NFκB into the nucleus and the translocation was inhibited by ISO and accelerated by PAX addition. These findings suggest that KCNMA1 influences CNS inflammation by promoting astrocytes to adopt a pro-inflammatory phenotype.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

NMOSDにおける脊髄病巣は長大であり、その対応としてはステロイドや血漿交換による炎症抑制しかなく、患者に重篤な障害を残すことが多い。再発を抑制することで障害の蓄積を抑制することは重要だが、急性期の障害進展を抑制する治療は限られている。BKチャネルはアストロサイト傷害時の炎症誘導に影響していると考えられ、同機構を介してCNSのグリア炎症を抑制し、障害度の緩和をもたらす可能性がある。