Application of anti-HMGB1 m Ab in intracerebral hemorrhage-induced brain injury in common marmoset and elucidation of HMGB1 translocation mechanism

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17930
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Okayama University
• Principal Investigator: WANG Dengli 岡山大学, 医歯薬学域, 助教 (40815693)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 抗体治療 / 脳出血 / HMGB1

Outline of Final Research Achievements

Intracerebral hemorrhage (ICH) is a critical medical issue without effective treatment. High mobility group box-1 (HMGB1) acts as an inflammatory cytokine when released from cell nuclei. Prior research showed that anti-HMGB1 monoclonal antibody (mAb) significantly reduced brain damage in a rat ICH model, leading to the development of a humanized version (OKY001) for clinical use. This study tested the humanized mAb in marmosets, finding that it blocked HMGB1 release and reduced brain iron deposition, oxidative stress, and brain injury size 12 days post-ICH. It also hindered hemoglobin uptake by macrophages, delaying the clearance of hemoglobin and its toxic byproducts. Additionally, it mitigated weight loss and enhanced behavioral outcomes post-ICH, suggesting its potential as a new ICH treatment.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

この研究は脳内出血（ICH）の治療法開発に新たな道を示し、HMGB1をターゲットとした治療が脳損傷を減少させる可能性を明らかにした。
効果的な治療法が患者の生活の質を向上させ、医療費の削減や社会復帰の促進に寄与することが期待される。