Komuro Issei, PhD, MD | The University of Tokyo Graduate School of Medicine; Nomura Seitaro, PhD, MD; Naito Mitsuru, PhD; Kimura Yasuaki, PhD; Yoshioka Kotaro, PhD, MD
Competition Sponsor: Japan Agency for Medical Research and Development
Awardee Year: 2024
The heart pumps blood throughout the body, but pathological stresses such as high blood pressure or myocardial infarction can impair its function, leading to heart failure. The incidence of heart failure is rapidly increasing, primarily due to an aging population, resulting in a global heart failure pandemic. Currently, approximately 64 million people worldwide suffer from heart failure and face life-threatening risks.
We pioneered the cardiac single-cell RNA-seq analysis to explore heart failure pathology in mice and humans. Our research highlighted DNA damage in cardiomyocytes as crucial (Nature Communications. 2018; Nature Cardiovasc Res. 2022; Science Adv. 2023; Circulation. 2024) and identified IGFBP7, secreted by damaged cardiomyocytes, as a key marker of severe heart failure (Nature Communications. 2022). We demonstrated that targeting IGFBP7 in the cardiac microenvironment is an effective treatment (Circulation. 2024). Additionally, we clarified heart failure-specific transcriptional mechanisms through single-cell multi-omics analysis and developed gene therapies targeting these mechanisms. We further developed a drug delivery system (DDS) with cardiac-specific ligands, without the need for adeno-associated virus vectors, while advancing nucleic acid technologies for improved gene suppression.
In this study, we aim to develop a new nucleic acid drug for heart failure that targets transcriptional regulation and the microenvironment in the heart. By combining heart failure-targeting molecules, drug delivery systems, and nucleic acid technologies, we seek to create the first drug addressing the molecular mechanisms of heart failure. This breakthrough aims to address a major health threat to the elderly and promote healthy longevity.