ZyVersa Therapeutics, Inc. announced publication of an article in the peer-reviewed journal, Diabetes, demonstrating that AIM2 and NLRP3 inflammasome activation contributes to development of atherosclerosis in two different animal models of type 1 diabetes. In the paper titled, ?Hematopoietic NLRP3 and AIM2 inflammasomes promote diabetes-accelerated atherosclerosis, but increased necrosis is independent of pyroptosis,? the authors studied mouse models of type 1 diabetes and atherosclerosis.

Following are key findings reported in the paper: Diabetic animals demonstrated activation of inflammasome pathways, based on increased levels of plasma IL-1ß and IL-18, and elevated levels of cleaved caspase- 1 in the peritoneal cavity fluid. Each of the two different type 1 diabetes models exhibited similar levels of plasma IL- 1ß and IL-18 and similar aortic lesion sizes and severity. Diabetic mice deficient in NLRP3 and/or AIM2 had reduced aortic lesion size compared to diabetic controls, indicating that NLRP3 and AIM2 inflammasome activation contributes to atherosclerotic lesion development.

Results are consistent with other animal model studies showing deficiencies in essential inflammasome components, such as NLRP3, AIM2, ASC, and caspase-1, appear to protect against atherosclerosis. IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response.

It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1ß early in the inflammatory cascade. IC 100 also binds to ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1ß and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases.

Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response.