Neuromedin B receptor antagonists as a novel treatment for Cushing's disease.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17481
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Hokkaido University
• Principal Investigator: Kameda Hiraku 北海道大学, 大学病院, 助教 (20826127)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: クッシング病 / ACTH / ニューロメジンB受容体

Outline of Final Research Achievements

In this study, using AtT-20 cells, a murine ACTH-producing cell line, we found that administration of the neuromedin B receptor antagonist PD168368 suppressed ACTH production, tumour growth and cyclin E gene expression. Administration of PD168368 to mice with thymic aplasia, transplanted AtT-20 cells subcutaneously, resulted in a decrease in blood ACTH and corticosterone, suggesting that PD168368 may also be effective when administered in vivo. In human ACTH pituitary adenoma cells, half of the cases showed decreased ACTH secretion after treatment with PD168368. These results suggest that a neuromedin B receptor antagonist may be a novel therapeutic agent for Cushing's disease.

Free Research Field

内分泌

Academic Significance and Societal Importance of the Research Achievements

本研究からニューロメジンB受容体がクッシング病の新規治療ターゲットとなりうること、経路として細胞周期関連蛋白、特にサイクリンEの抑制を介することが初めて示された。クッシング病では手術で寛解に至らない場合の薬物治療薬の選択肢が限られており、ニューロメジンB受容体拮抗薬が将来的にクッシング病の新規治療薬として開発を進めることで、クッシング病患者のQOLの改善に貢献できる可能性がある。