The blood-brain barrier of Lambert-Eaton myasthenic syndrome with paraneoplastic cerebellar degeneration has failed

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09787
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagasaki Institute of Applied Science
• Principal Investigator: MOTOMURA MASAKATSU 長崎総合科学大学, 工学研究科, 教授 (70244093)
• Co-Investigator(Kenkyū-buntansha): 白石 裕一 長崎大学, 病院(医学系), 講師 (40423644) ; 吉村 俊祐 長崎大学, 病院(医学系), 助教 (70746635)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: ランバート・イートン筋無力症症候群 / 傍腫瘍性小脳変性症 / 血液脳関門 / GRP78抗体

Outline of Final Research Achievements

The aim of this study is to elucidate the pathogenic mechanism of cerebellar ataxia in patients with Lambert-Eaton myasthenic syndrome with paraneoplastic cerebellar degeneration (PCD-LEMS) . The method was examined cytobiologically by reacting the endothelial cells of human blood-brain barrier (BBB) with immunoglobulin G (IgG) of PCD-LEMS patients and LEMS patients. As a result, IgG in PCD-LEMS patients disrupted BBB, but there was no change in IgG in LEMS patients. Furthermore, glucose-regulated protein 78 (GRP78) antibodies were identified as an antibody candidate that impairs BBB function from IgG in PCD-LEMS patients (Shimizu et al, 2019).

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的な意義は、これまで未解決であった傍腫瘍性神経症候群の発症機序を明解に解決できる点である。現時点では、血液脳関門(BBB)に障害を与える自己抗体は証明されておらず、多発性硬化症や視神経脊髄炎など神経難病の発症機序の解明に役立つ仕事になることが予想される。また、本研究の社会的な意義は、治療困難なPCD-LEMSを含む傍腫瘍性神経症候群の治療を抜本的に変え、患者さんに多くの恵みをもたらすことが期待される。