A newly developed compound that reduces harmful inflammation in rats caused by overactive neutrophils shows great potential as a safer treatment for various inflammatory diseases in humans. Neutrophils are the most abundant type of white blood cells in the human body, and they play a crucial role in immune response. These immune cells help fight infections by engulfing pathogens and releasing enzymes that kill the invaders.
But although they're essential for fighting infections, neutrophils can also become overactive, leading to various inflammatory diseases. When they are activated by infection, neutrophils can release neutrophil extracellular traps (NETs), web-like structures consisting of DNA and proteins, which trap and kill pathogens as a part of the normal host defense mechanism. However, too much NET formation can significantly damage tissues, thus contributing to inflammation.
A team of researchers from Hokkaido University and Alivexis, Inc., investigated a recently-developed drug candidate, MOD06051, which reduces harmful inflammation in rat models by targeting neutrophils. The results of their joint research were recently published in Nature Communications.
We found that MOD06051 works as a selective inhibitor for Cathepsin C (CatC), a key regulator that activates multiple enzymes inside of neutrophils known as neutrophil serine proteases (NSPs). One such NSP is neutrophil elastase, an enzyme involved in killing pathogens but also an essential factor for NET formati.