InflammX Technology

The NLRP3 inflammasome is a multiprotein innate immune complex that forms inside cells. The inflammasome pathway of inflammation is a relatively new discovery, first described in 2002. Since then it has become a major target for therapeutic intervention since inflammasome mediated autoinflammation has been shown to be a common pathway of pathology in multiple disease states. The inflammasome has two triggering signals, a priming signal (the initial insult) which is unpredictable and beyond an organism’s control. This leads to an activation signal that enables assembly of inflammasome complexes, resulting in the activation of multiple pro-inflammatory cytokines and downstream pathology to affected tissues. If not terminated, these dynamic immune responses contribute to long lasting autoinflammatory disease. The InflammX drugs in development, regulate upstream activation signaling, breaking the persistent autoinflammation that is a feature of those diseases. 

Connexin43 (Cx43) hemichannels continuously form in the cell membrane of most of the organs of our body. They have one physiological function in life, which is to remain closed in the cell membrane until they dock with another Cx43 hemichannel on an adjoining cell. At this point both open to create the communication portal between cells called the Gap Junction.

In the presence of pathological stimuli, Cx43 hemichannels crowd the cell membrane and open prematurely, before docking with hemichannels on adjoining cells. Prematurely open Cx43 hemichannels, facilitate the release of ATP into the extracellular space. The ongoing release of extracellular ATP signals the activation of the NLRP3 inflammasome resulting in a perpetuated cycle of inflammation. This cycle precipitates further release of ATP and activation of pro-inflammatory cytokines. This leads to autoinflammation. resulting in significant tissue damage including ischemia, microvascular leak, edema, microvascular dropout, and if left untreated, fibrosis.

 Xiflam™, breaks the cycle of inflammasome mediated autoinflammation by closing prematurely open Cx43 hemichannels, reducing and ultimately preventing the release of extracellular ATP and the signal for continued inflammasome activation. Since Xiflam acts to specifically access and close pathologically open Cx43 hemichannels shutting down the signaling of the inflammasome, patients remain immunocompetent.