A novel therapy for sepsis in the intensive care setting

Sepsis is a life-threatening syndrome that arises when the body’s immune response to infection becomes dysregulated, leading to organ failure and ultimately death. Globally, sepsis affects millions of people every year and is responsible for up to 20% of deaths worldwide. In the Netherlands alone, tens of thousands of people suffer from sepsis each year, leading to high rates of ICU admissions, long-term complications and deaths. New, effective treatments are urgently needed. The HistoSeps project addressed this challenge by establishing a public-private partnership between Amsterdam UMC, Maastricht University, and Matisse Pharmaceuticals to explore a novel therapy for patients with sepsis.

The project focused on M6229, the low-anticoagulant molecule fraction of unfractionated heparin, which is a well-known and widely used anticoagulant. M6229 is able to neutralize cell-free histones—proteins that are released into the bloodstream when cells are damaged and which are believed to play a major role in organ failure in patients with sepsis – while exerting lower anticoagulant effects in comparison to regular unfractioned heparin. By targeting and binding to these toxic proteins, M6229 may reduce inflammation and limit organ failure.

A first-in-human, phase 1 trial was conducted in 10 critically ill patients with sepsis, administering M6229 via a six-hour intravenous infusion. The results showed that the drug was safe, well tolerated, and associated with reductions in inflammatory markers such as CRP, IL-6, IL-8, IL-17, CCL2 and CCL4. While further research is necessary, these findings are encouraging and support continued investigation.

Future steps include larger trials to confirm these results. If proven effective, M6229 could become a valuable new treatment to improve outcomes for patients with sepsis, one of the most urgent challenges in intensive care medicine.