ZyVersa Therapeutics Announces Publication That Demonstrates Role of Inflammasome Activation in Hypertrophic Heart Disease Induced by Mechanical Stress

ZyVersa Therapeutics, Inc. recently announced publication of an article in the peer-reviewed journal Circulation demonstrating the role of inflammasome NLRP3 activation in hypertrophic heart disease induced by mechanical stress.

In the paper titled NLRP3 Inflammasome Activation Through Heart-Brain Interaction Initiates Cardiac Inflammation and Hypertrophy During Pressure Overload, data are reported from in vivo studies in various animal models, and in vitro experiments using primary rat neonate cardiomyocytes and fibroblasts, and a human microvascular endothelial cell line. The objective was to determine the regulatory mechanism of inflammation and its role in the stressed heart. Key findings are as follows:

• Neural signals contribute to NLRP3 inflammasome activation in cardiac nonimmune cells that initiate inflammation in the stressed heart through IL-1β production
• Pressure overload to the heart’s left ventricle activates sympathetic efferent nerves (SENs) to secrete extracellular ATP, which activates NLRP3 inflammasomes in cardiomyocytes, fibroblasts, and vascular endothelial cells, leading to L-1β production and initiation of the inflammatory cascade that causes cardiac adaptive hypertrophy in response to mechanical stress
• Cardiac afferent nerve signals also contribute to ATP secretion from SEN terminals and inflammasome activation
• The above findings reveal that cardiac inflammation and hypertrophy are controlled through NLRP3 activation through heart-brain interactions

To read the article, Click Here.

“The research published in Circulation demonstrating that mechanical stress on the heart, such as high blood pressure, initiates NLRP3-induced inflammation through heart-brain interactions causing hypertrophic heart disease, provides support for Inflammasome ASC Inhibitor IC 100 as a potential therapeutic candidate for a condition that affects approximately 1 in 500 people. Hypertrophic heart disease puts people at greater risk of heart failure, stroke, and cardiac arrhythmias, including sudden cardiac death. Our preclinical data demonstrate that IC 100 has broad penetration, including the heart and central nervous system, where it can inhibit formation of NLRP3 and other types of inflammasomes to block initiation of the inflammatory cascade. Likewise, IC 100 uniquely inhibits ASC specks to block perpetuation of damaging inflammation,” said 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.

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.

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, visit www.zyversa.com.