Elucidation of the pathogenesis of axial spondylitis and spinal ankylosis using mouse models of spondyloarthritis and development of new therapies.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16674
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tohoku University
• Principal Investigator: Izumiyama Takuya 東北大学, 大学病院, 助教 (00844276)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脊椎関節炎 / 体軸性関節炎 / SKGマウス / JAK阻害薬 / バリシチニブ / 付着部炎 / 脊椎強直

Outline of Final Research Achievements

SKG mice developing lesions spondyloarthritis-like were treated with a JAK inhibitor (Balicitinib) and compared to a control group. The dosing regimen was 60 mg/kg/week subcutaneously in a continuous dose using an Alzet osmotic pump. When comparing the treatment group (n=9) with the control group (n=11), significant differences were found in arthritis scores (p=0.007) and pathology scores of the right and left ankle joints (p=0.02, p<0.001). There was also an improvement in peri-spinal enthesitis, which is being statistically analyzed. Additional measurements of serum cytokines and immunostaining for histology are being investigated in preparation for submission to the journal.

Free Research Field

関節リウマチ、脊椎関節炎

Academic Significance and Societal Importance of the Research Achievements

脊椎関節炎は脊椎強直や破壊性末梢関節炎によりADLを著しく障害する進行性疾患である。早期からの治療介入が望まれるが、一方で疾患の成因や発症のメカニズムは未解明な部分が多い。Janus kinase (JAK) 阻害剤は関節破壊抑制に有用だが、脊椎関節炎の強直性病変、骨化病変抑制に対する効果は確定されていない。そこで脊椎関節炎のモデルマウスとされるSKGマウスを用いてJAK阻害剤の効果を解析し、体軸性脊椎炎の病変の抑制効果を示すことができた。これは脊椎関節炎に対する新規の薬剤適応や、骨化のメカニズムの解明につながる可能性を示唆する、重要な知見と考える。