Development of a novel immunomodulatory therapy for cardiac inflammation

Immunomodulatory treatments against cardiac inflammation in myocardial infarction (MI), myocarditis and sepsis do not currently exist.

The alarmin S100A9 is released in large amounts in MI, and also participates in the pathogenesis of myocarditis and sepsis.

We have shown that S100A9 blockade has beneficial therapeutic effects in MI.Our experimental aim is to characterize the innate immune mechanisms triggered by S100A9 and to design treatment strategies based on S100A9 blockade to inhibit inflammation and improve cardiac function in diseases with a cardioinflammatory component.

In the clinical arm, we aim to identify novel soluble molecules for risk evaluation and follow-up in MI and sepsis patients.

We will study the influence of S100A9 blockade on cardiac function and inflammation in animal models of MI, myocarditis and sepsis and we will examine the underlying immune mechanisms. We will use the acquired knowledge to devise optimal treatment strategies.

In a prospective study on a large cohort of MI patients, we will explore how the dynamics of immune mediators in plasma from the inflammatory to the recovery phase correlate with cardiac recovery and prognosis. The relationships between S100A9 and post-sepsis prognosis will also be assessed.

A therapy reducing inflammatory myocardial damage could improve morbidity and mortality in MI, myocarditis and sepsis patients. Novel specific markers are needed to identify treatment candidates and to monitor efficacy.