ELD680, systemic inflammation

Calcium signaling controls multiple functions of immune cells, including B and T cells, macrophages, neutrophils, and mast cells. Dysregulation of calcium signaling can alter these functions and has been associated with various autoimmune diseases. Additionally, immune responses to certain pathogens can lead to systemic inflammation.

An example of systemic inflammation is sepsis, which is a life-threatening clinical condition that results from a dysregulation of host immune responses to infection and leads to multi-organ failure. Sepsis occurs in 1.7 million US adults annually, resulting in hospitalizations and 270,000 deaths. Of those that survive, nearly 50% of sepsis patients are re-hospitalized, and one in six survivors does not survive past one year. Sepsis is characterized by increased bacteremia, resulting in systemic hyper-inflammation and a failure to normalize immune homeostasis, resulting in septic shock. Treatment consists of antibiotics to target bacterial infections and supportive care for targeted organs. However, no drugs are currently available to target and treat the hyper-immune response, indicating that there is a critical unmet need for progressive sepsis therapies.

Our goal is to develop an intravenously delivered anti-inflammatory peptide that can improve outcomes in sepsis and other systemic inflammatory diseases. ELD680 is a Ca2+ channel antagonist designed to be stable in the blood. Following LPS exposure that resulted in inflammatory responses, we found that ELD680 reduced neutrophilia and inflammation in the blood.

Mice were exposed to E. coli LPS intravenously to elicit an inflammatory response, followed by ELD680.   ELD680 significantly elevated blood monocyte levels and reduced blood neutrophil levels 24 h later. These data indicate that ELD680 can reduce systemic inflammation.   ”