Science
Calprotectin (S100A8/A9) is a potent pro-inflammatory protein that increases rapidly in the blood after MI, reaching up to 10 times normal values. Calprotectin activates the innate immune receptors TLR4 and RAGE and is a potent early trigger of the inflammatory cascade. Calprotectin leads to excessive inflammation in the heart and has a direct inhibitory effect on heart cell function. Clinical studies have shown that high levels of calprotectin in patient blood are associated with increased risk for heart failure and recurrent MI.
Calprotectin has a central role in the inflammatory phase of MI, by stimulating:
- immune cell production in the bone marrow and spleen
- neutrophil and monocyte exit from the bone marrow and spleen into the blood
- neutrophil and monocyte recruitment from the blood into the myocardium
CAL-001 binds calprotectin directly, preventing the activation of its receptors.
CAL-001 inhibits local and systemic inflammation and promotes repair, leading to improved heart function.
Preclinical results in MI
Our calprotectin blocker has shown good tolerability and pharmacological properties in mice, and a good toxicology profile in-vitro. We tested the effects of calprotectin blockade during the inflammatory phase in mice with induced MI. A three-day treatment reduced the presence of inflammatory cells in the heart by 30% and significantly improved cardiac function compared to controls (25% vs 16% average ejection fraction by day 21). The treatment also improved cardiac function when combined with coronary revascularization (48% vs 35% average ejection fraction by day 21). Cardiac output improved to 80% of pre-MI levels in mice receiving calprotectin blockade but remained low in controls (15.7 mL/min vs 11.1mL/min on day 21).