Drug development for infantile hemangioma through manipulation of the ubiquitin E3 ligase complex

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15718
• 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: Ehime University
• Principal Investigator: Kagajo Mari (手束) 愛媛大学, 医学部附属病院, 医員 (40527511)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 血管腫 / 血管新生阻害剤 / アプタマー

Outline of Final Research Achievements

Excessive cell proliferation of endothelial cells as well as abnormal angiogenesis cause hemangioma. The inhibition of angiogenesis, thus, would be a therapeutic option of hemangioma. To data, most anti-angiogenic drugs only target vascular endothelial growth factor (VEGF) or its receptors. In this study, making use of the exponential enrichment (SELEX), we developed 15 single-stranded deoxyribonucleic acid (ssDNA) aptamers capable of binding to CBF1 with high affinity (Kd; 10-300 nM), named as Apt-1 to Apt-15. Among them, Apt-3, inhibited angiogenesis through the activation of Notch signaling in vitro. Apt-3 may contribute to the development of a novel angiogenic inhibitor.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

血管腫 (ヘマンジオーマ)は、血管内皮細胞の異常増殖が原因で乳幼児期に発症する。肝臓等の臓器に腫瘍形成が見られる重症例では、外科的手術や肝移植などが必要となる。また、皮膚に腫瘍が形成される軽症例では容姿に影響を与え、患者のQuality of Lifeを低下させる。しかし、その特異的な薬物治療法は確立されていない。本研究が開発した血管新生阻害活性を有するCBF1結合DNAアプタマーはヘマンジオーマを含めた血管新生関連疾患の新しい治療薬のシーズとなる可能性を秘めている。