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BIO19344-T1

NEUTRALIZING GRANZYME B FOR PROVIDING CARDIOPROTECTION IN A SUBJECT WHO EXPERIENCED A MYOCARDIAL INFARCTION

The present invention relates to a method for providing cardioprotection in a subject who experienced a myocardial infarction comprising administering the subject with a therapeutically effective amount of a Granzyme B inhibitor. Here, the inventors show that following acute MI in mice, CD8+ T lymphocytes are quickly recruited and activated in the ischemic heart tissue, and release Granzyme B leading to cardiomyocyte apoptosis and deterioration of myocardial function. Antibody-mediated (CD8specific antibody) depletion of CD8+ T lymphocytes decreases Granzyme B content and apoptotic within the myocardium and inflammatory response. mAb mediated-CD8 depletion limits myocardial injury and improves heart function. These effects are recapitulated in mice with CD8+ T cell selective Granzyme B deficiency in mice. Granzyme B is also produced by other cell types such as NK cells. Global Granzyme B deletion (GzmB-/- mice) decreases apoptotic within the myocardium, reduces local pro-inflammatory signature and ultimately limits infarct size after MI. The inventors also show that elevated circulating levels of Granzyme B in patients with acute MI predict increased risk of death at 1-year follow-up. The work unravels a previously unsuspected pathogenic role of Granzyme B following acute ischemia, and identifies novel therapeutic targets for this devastating condition.


Keywords : -
Patent Application number : 19306002.7
Patent Application date : 2019-08-02
Multidisciplinary field : -
Technology/Engineering : -
Technological Platform : -
Rare disease : -
Second indication : -
Inventors : -
Publications :
  • In progress

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