- Lupus Nephritis (“LN”) is characterized by inflammation in the kidney, protein leakage into the urine (“proteinuria”), and progressive kidney damage
- NLRP3 inflammasomes were extensively activated in the kidneys of LN patients, with higher levels of activation in patients with more severe forms of the disease
- Inflammasome activation was positively correlated with clinicopathological indices of LN
- ZyVersa is developing Inflammasome ASC Inhibitor IC 100, which can inhibit up to 12 different inflammasomes (including NLRP3 inflammasomes) and their associated ASC specks which perpetuate damaging inflammation
WESTON, Fla., June 28, 2023 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, announces publication of an article in the peer-reviewed journal, Clinical Immunology, demonstrating the role of inflammasome NLRP3 activation in lupus nephritis.
In the paper titled, “Renal NLRP3 Inflammasome activation is associated with disease activity in lupus nephritis,” the authors evaluated renal biopsy tissue of patients with biopsy proven LN in comparison to control tissue. Data demonstrated that renal NLRP3 inflammasome activation positively correlated with LN severity and clinicopathological indices of LN. Following are key findings reported in the paper:
- Expression patterns of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in the glomeruli and tubulointerstitum of LN patients were significantly higher in LN patients versus controls
- Levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 were higher in patients with proliferative (more severe) LN than in patients with non-proliferative LN
- Levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 were positively correlated with several clinicopathological indices, including, proteinuria, renal pathological activity indices, and systemic lupus erythematosus disease activity index (SLEDAI) scores
The authors stated, “We comprehensively evaluated the activation patterns of the NLRP3 inflammasome pathway in the renal tissues of LN patients. NLRP3 was extensively activated in various renal intrinsic cells and infiltrating cells, and was closely associated with disease activity, which needs further explorations.” To read the article, Click Here.
“The research published in the Journal of Clinical Immunology demonstrated that renal NLRP3 inflammasome activation is associated with lupus nephritis disease activity, providing support for inflammasome inhibition as a promising treatment for LN. Unlike NLRP3 inhibitors, which only inhibit formation of the NLRP3 inflammasome to block initiation of the inflammatory cascade, Inflammasome ASC inhibitor IC 100 inhibits formation of multiple types of inflammasomes, and it uniquely inhibits ASC specks to block perpetuation of damaging inflammation,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here.
About Inflammasome ASC Inhibitor IC 100
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-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β 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.
About ZyVersa Therapeutics, Inc.
ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com.
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