Development of early detection method for adriamycin-induced cardiomyopathy based on the immunosenescence

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Hokkaido University
• Principal Investigator: Ishimori Naoki 北海道大学, 医学研究院, 特任准教授 (70399848)
• Co-Investigator(Kenkyū-buntansha): 横田 卓 北海道大学, 大学病院, 特任講師 (90374321) ; 加畑 馨 北海道大学, 大学病院, 講師 (00399867)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 心不全 / 慢性炎症 / 薬剤性心筋障害

Outline of Final Research Achievements

Rapid aging has been progressing in our country, with one in two citizens expected to develop cancer in their lifetime. Among classical cancer treatment drugs, some exhibit cardiotoxicity, such as anthracycline-based agents, which can lead to refractory heart failure and occasionally death when administered in high doses. We have elucidated that chronic inflammation is involved in the development mechanism of drug-induced cardiomyopathy.
In recent years, the introduction of new drugs such as molecular targeted drugs has significantly improved the outcome of cancer treatment, leading to a sharp decrease in the frequency of use of cancer treatment drugs with serious side effects such as cardiotoxicity. However, our understanding of the pathogenesis of classical drug-induced cardiomyopathy may be crucial as it could lead to novel therapeutic targets for heart failure treatment.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

アントラサイクリン系抗がん剤は、リンパ腫・乳がんに対する基本的治療薬であったが、用量依存的に心筋障害を合併するため、副作用が軽微な分子標的薬などを用いる治療プロトコルに移行しつつある。我々の薬剤性心筋障害モデルを用いた基礎研究の知見で、慢性炎症を制御することで心筋障害を軽減するという、心不全の新たな治療の可能性が示唆された。我々は免疫調節細胞であるナチュラルキラーT細胞を活性化する糖脂質α-ガラクトシルセラミドの薬剤性心筋障害に対する抑制効果に関する用途特許を取得した。これらの一連の研究成果は、心不全に対する新たな治療薬の開発につながる可能性があり、学術的にも社会的にも大きな意義がある。