Development of a novel therapeutic strategy for the treatment of spinal cord injury by modulating sphingosine 1-phoshate metabolism

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10835
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Jichi Medical University
• Principal Investigator: Kimura Atsushi 自治医科大学, 医学部, 准教授 (20364507)
• Co-Investigator(Kenkyū-buntansha): 白石 康幸 自治医科大学, 医学部, 助教 (50646338) ; 大森 司 自治医科大学, 医学部, 教授 (70382843)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脊髄損傷 / 生理活性脂質 / スフィンゴシン1リン酸

Outline of Final Research Achievements

Here, we investigated whether modulation of sphingosine 1-phosphate (S1P) lyase enhances functional recovery after spinal cord injury (SCI). We employed a mouse contusion SCI model, induced by the Infinite Horizons impactor using a force of 60 kdyn at the level of T10. Functional outcome was assessed with the Basso Mouse Scale. Mice were divided into two groups: Mice treated with per os administration of 4-deoxypyridoxine (DOP), a S1P lyase inhibitor, via drinking water at a concentration of 50 mg/L and saline-treated control mice.
Mice treated with DOP showed significantly better BMS score compared with that of control mice. A proteome cytokine array analysis revealed that DOP-treated mice show significantly decreased expression of inflammatory cytokines, including TNFα, IL-27, CCL-1, G-CSF, IL-13, IL-1β, IL-23, and CXCL-9. These results suggest that inhibition of S1P lyase can be a novel therapeutic strategy for the treatment of SCI.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

脊髄損傷に対する薬物治療は選択肢が限られており、本研究はスフィンゴシン1-リン酸とその代謝経路がその治療標的となり得る点を示した点で意義があると考えられる。今後S1P lyase阻害剤の投与法と投与時期を最適化すること、また同様の作用を持つ他の薬物の効果についてもさらなる検討が待たれる。