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H2020Individual fellowship2019–2021

ZeNewCardio · Discovering Heart Regeneration Therapies Through Zebrafish

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2019-06-01 → 2021-05-31
EU contribution
€160,932
Participants
1
Scheme
MSCA-IF-EF-SE

Lines connect the coordinator with its partners.

Results in brief

ZeNewCardio: Discovering Heart Regeneration Therapies Through Zebrafish

Myocardial infarction (MI) is one of the leading causes of death worldwide. In 2020, MI is estimated to have affected around 126 million people (approximately 1.8 % of world’s population). Individuals suffering from heart attacks die immediately or within days of the event. Unfortunately, a very high percentage of survivors also die in later years (~ 30%). This is mainly due to the development of heart failure since damaged human cardiac tissue is not able to recover its structure and function after damage. Regenerative medicine aims at improving the function of the infarcted heart in order to avoid or reduce the possibility of developing heart failure. Interestingly, unlike mammals which show insufficient regenerative capacity, the zebrafish, an emerging research organism in translational research, has the lifelong ability to fully recover their myocardial function upon injury. The ZeNewCardio project has been focused on the development of strategies to discover potential mechanisms activating cardiac regeneration conserved between fish and humans. We aimed to use the gathered knowledge to open new therapeutic venues for human infarction. The results have revealed novel regulators of myocardial recovery and have led to the development of compounds with potential pro-regenerative effects on injured mammalian hearts.

Data: CORDIS, © European Union

Project objective

Ischemic heart disease is a leading cause of death worldwide. However, heart transplantation is risky, plus the number of donors does not cover the demand of patients, and alternative treatments are inefficient. Given that adult mammalian hearts display insufficient regeneration capability to allow complete myocardial recovery, a promising treatment after infarction could be the identification of molecules unblocking cardiac self-healing/regeneration. In that sense, zebrafish displays life-long ability to regenerate its heart after damage. Interestingly, the same genetic programs promoting cardiomyocyte dedifferentiation and proliferation after injury in zebrafish are present, albeit dormant, in the adult mammalian heart. This makes zebrafish a powerful model to unravel key molecular pathways that might induce heart regeneration in humans, if activated. Here, we propose the development of ZeNewCardio: a high-throughput preclinical platform using the zebrafish model to find suitable treatments for heart regeneration after ischemia. The project aims are: 1) to implement cardiac injury models in zebrafish; 2) to use these models to identify genes involved in heart regeneration, with a focus on genes enabling cardiomyocyte dedifferentiation/proliferation; 3) to use the gathered knowledge to discover novel cardiac pro-regeneration drug therapies applicable to humans. Our genetic and analysis tools will speed-up the process of target validation of novel gene regulators of regeneration, based on the stimulation of endogenous regenerative responses, and the discovery of new drug therapies to treat or protect ischemic hearts.

Original text from CORDIS.

Participants

  • ZECLINICS SL · SANT FELIU DE LLOBREGATCoordinatorSpain

Links

Data: CORDIS, © European Union