NEWHEART · From Naked Mole-Rat to Preclinical Pig: Advancing a Regenerative Factor for Myocardial Infarction

Cardiovascular disease is the leading cause of death worldwide, and myocardial infarction (MI) results in permanent loss of cardiomyocytes, fibrotic scarring, and progression to heart failure. Current therapies primarily limit damage, prevent adverse remodeling, and relieve symptoms, but they do not restore lost myocardium or induce true regeneration, leaving a major unmet clinical need. We have established the naked mole-rat as the first adult mammal capable of true cardiac regeneration, characterized by scar resolution, cardiomyocyte proliferation, and functional recovery. This unique model provides an unprecedented opportunity to discover factors that promote regeneration in the adult heart. Using this approach, we identified a previously uncharacterized, injury-activated extracellular matricellular protein, uniquely present in the naked mole-rat injured zone, which shows pro-regenerative and anti-fibrotic effects in vitro. This PoC proposes to develop this factor as an off-the-shelf regenerative therapy post-MI, delivered via anterograde administration during reperfusion, in alignment with existing clinical practices such as angioplasty. The therapy aims to stimulate cardiomyocyte renewal, limit fibrosis, and orchestrate repair pathways in the adult heart. The factor will be evaluated in a pre-clinical porcine MI model to generate critical data on efficacy in promoting regenerative repair and preventing fibrosis, as well as preliminary systemic safety. These data will provide the necessary evidence to support commercialization and regulatory strategy. To advance translation, the project will secure strong IP protection, early stakeholder engagement, and partnerships with clinical and commercial experts. By offering a context-specific regenerative therapy integrated with current care pathways, this approach has the potential to transform post-MI treatment and prevent heart failure, addressing a critical unmet medical need.