Novel therapeutic strategy targeting RAGE for treatment of peripheral neuropathy and visceral pain

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Kindai University
• Principal Investigator: Kawabata Atsufumi 近畿大学, 薬学部, 教授 (20177728)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 疼痛の発生・増強機序 / RAGE / HMGB1 / 末梢神経障害 / 内蔵痛

Outline of Final Research Achievements

To develop seeds for development of medicines targeting RAGE for treatment of intractable pain, the present study first ascertained the involvement of RAGE in neuropathic and visceral pain using animal models. We then demonstrated that middle-molecular-weight-heparinylphenylalanine suppressed intractable pain possibly through selective blockade of RAGE. Our in silico analysis identified a small molecule compound that inhibits AGE-RAGE binding and is useful as a seed compound for novel RAGE blocker development. Together, our study identified both large and small molecules as RAGE blockers, which would be useful for pain treatment.

Free Research Field

神経・疼痛・炎症薬理学

Academic Significance and Societal Importance of the Research Achievements

これまでに、アルツハイマー病の予防・治療を目的とするいくつかのRAGE拮抗薬の開発が試みられてきたが、まだ臨床応用には至っていない。本研究では、RAGEが難治性疼痛の治療標的分子になりうることを証明して、高分子および低分子のRAGE拮抗薬のシーズを得ることができた。現在、モルヒネ、プレガバリンなどが効かない難治性慢性疼痛を訴える患者が多数存在することを考慮すると、今回得られた知見は社会的にもインパクトのあるものであると考える。