Development of novel treatment for neonatal hypoxic-ischemic encephalopathy using phage display method

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16922
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Higuchi Asuka 滋賀医科大学, 医学部, 客員助教 (90613480)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 新生児低酸素性虚血性脳症 / 脳性麻痺

Outline of Final Research Achievements

To develop a novel therapeutic approach for neonatal hypoxic ischemic encephalopathy (HIE), we have created a therapeutic peptide (MG1-KLA) by binding a peptide that selectively binds to M1 microglia with inflammatory activity (MG1) to a peptide that induces apoptosis (KLA) using a phage display method and examined its therapeutic effect. In vitro, we were able to confirm that MG1-KLA selectively induces M1 microglia to apoptosis.
By using a hypoxic chamber with auto-regulated temperature during the creation of HIE model mice, we found that even a small change of 0.5℃ produced a significant difference in pathology and behavior in a neonatal mouse model of HI brain injury. Furthermore, there was a correlation between ambient temperature and microglial accumulation.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

HIEの新規治療法開発を目指し、炎症活性を有するM1ミクログリアを治療標的とした研究を行った。In vitroでの治療用ペプチドによる治療効果を確認できたので、今後はHIEマウスにペプチドを投与し、治療効果の検討を行っていく。HIEマウスは重症度にばらつきが大きいとされるが、我々のモデルでは、0.5℃というわずかな環境温度変化とHIEの重症度の間に相関を認め、今後の本領域における研究の発展の基礎を築くことができた。