- Paper reports that obesity exacerbates scarring of the heart’s muscular tissue (myocardial fibrosis) through recruitment of inflammasome ASC to the heart’s mitochondria, facilitating NLRP3 inflammasome assembly and activation leading to damaging inflammation
- Obesity, which affects over 650 million adults, is a known risk factor for myocardial fibrosis which is associated with almost all heart diseases
- ZyVersa is developing Inflammasome ASC Inhibitor IC 100, designed to inhibit formation of multiple types of inflammasomes and their associated ASC specks to attenuate initiation and perpetuation of damaging inflammation
WESTON, Fla., Oct. 25, 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 a publication in the peer-reviewed journal, Diabetes, demonstrating the role of ASC in myocardial fibrosis induced by obesity. ASC is an inflammasome adaptor protein that has a critical role in inflammasome activation.
In the paper titled, “Obesity enables NLRP3 activation and induces myocardial fibrosis via hyperacetylation of HADHa,” the authors performed MRIs on obese and lean people and evaluated their plasma. They also studied an animal model of obesity, with and without induced myocardial injury. Data indicate that:
- Activated NLRP3 inflammasomes leading to increased levels of proinflammatory IL-1β and IL-18 contribute to obesity-related myocardial fibrosis in obese humans and mice.
- Inflammasome ASC localized in the heart’s mitochondria participates in NLRP3 inflammasome formation and activation based on mouse data.
- Inhibition of NLRP3 activation or removal of IL-1β and IL-18 abated the adverse effects on cardiac fibrosis and function in mice.
The authors concluded that these results provide new evidence for the involvement of mitochondria-localized ASC in obesity-induced cardiac fibrosis. To read the article, Click Here.
“Obesity, a well-established risk factor for cardiovascular disease, has reached pandemic proportions, and may affect up to two-thirds of the adult population in developed countries,” stated Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “The research published in Diabetes demonstrates that ASC in the heart’s mitochondria facilitates NLRP3 inflammasome assembly and activation leading to damaging inflammation and myocardial fibrosis associated with obesity. This provides support for Inflammasome ASC Inhibitor IC 100 as a potential therapeutic option. By inhibiting ASC, IC 100 blocks formation of NLRP3 and other types of inflammasomes to block initiation of the inflammatory cascade. Likewise, IC 100 uniquely inhibits ASC specks to attenuate perpetuation of damaging inflammation." 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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