Development of a novel neuroprotective drug by optimizing VCP compounds

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09449
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Yamagata Prefectural Yonezawa University of Nutrition Sciences (2021-2022); Hokkaido University (2020)
• Principal Investigator: Funaki Tomo 山形県立米沢栄養大学, 健康栄養学部, 助手 (10647192)
• Co-Investigator(Kenkyū-buntansha): 中川 慎介 福岡大学, 薬学部, 准教授 (10404211) ; 角家 健 北海道大学, 医学研究院, 特任准教授 (30374276) ; 周東 智 北海道大学, 薬学研究院, 教授 (70241346)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 神経保護薬 / 脊髄損傷 / 血液脊髄関門

Outline of Final Research Achievements

Through the screening of 2,400 compounds,14 analogues of VCP compounds were found to have a protective effect on cultured human brain vascular endothelial cells. Their protective effect was confirmed in a dose dependent manner. The study of intraperitoneal administration of one representing VCP compound to mice with spinal cord injury demonstrated that its blood concentration could reach the effective dose in vitro, that no apparent side effects occurred, and that the leakage of IgG area around the injury site was attenuated, suggesting that this VCP compound has a potential to protect blood spinal cord barrier after spinal cord injury. However, 8 weeks study of functional and histological analysis revealed no therapeutic effect of this compound on injured spinal cord. By optimizing the compound and the administration method, The VCP compound could be neuroprotective against spinal cord injury.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

VCP化合物は北海道大学独自の化合物であり、培養ヒト脳血管内皮細胞に対する濃度依存的細胞保護作用、および、脊髄損傷後の血液脊髄関門保護作用など、脊髄損傷に対する新規神経保護薬としての可能性を示した。長期的には、マウス脊髄損傷に対する治療効果が得られなかったが、本化合物自体の最適化、至適投与方法の検討により、脊髄損傷に対する新規神経保護薬の開発が期待できる。