Gelsolin decreased microparticle-driven inflammation and mitigated activation of the NLRP3 inflammasome in type 2 diabetes.
Low levels of gelsolin identified in individuals with type 2 diabetes living below poverty.
NORTH BRUNSWICK, N.J., April 13, 2023 (GLOBE NEWSWIRE) — BioAegis Therapeutics, Inc., a clinical-stage company developing therapies for inflammatory diseases through a portfolio built around plasma gelsolin (pGSN), a highly conserved and abundant endogenous human immune regulatory protein, announces publication of two new research studies exploring gelsolin’s role in type 2 diabetes, an inflammation-related metabolic disease.
The research study, Blood-Borne Microparticles Are an Inflammatory Stimulus in Type 2 Diabetes Mellitus, was led by Dr. Stephen R. Thom at the University of Maryland School of Medicine and supported by grants from the National Institute of Health and the US Office of Naval Research. It explored the role of microparticles (MPs) which drive inflammation in individuals with diabetes.
Type 2 diabetic subjects with foot ulcers were shown to have up to 14-fold elevations of blood-borne F-actin-coated microparticles. The study further found that these MPs contained IL-1 beta which indicated the activation of the NLRP3 inflammasome. Recombinant gelsolin supplementation in mice reversed this NLRP3 inflammasome-triggered process. It inhibited neutrophil activation and reduced actin-coated MPs produced by neutrophils under the oxidative stress caused by hyperglycemia.
Hyperglycemia-associated MPs activate neutrophils and this action is inhibited by rhu-pGSN. This work extends previous studies by Thom demonstrating that gelsolin at physiological levels removes F-actin from MPs and reduces MP numbers in other conditions.
These observations may be clinically important findings, as plasma gelsolin levels have been reported to decrease by nearly 50% in patients with type 2 diabetes and in mice rendered diabetic by streptozotocin treatment (1). These decreased gelsolin levels may account for ongoing inflammation in diabetes.
A second study, Plasma Gelsolin Levels Are Associated With Diabetes, Sex, Race, and Poverty in the Journal of Translational Medicine, was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, to understand gelsolin in a racially diverse population with and without Type 2 diabetes.
In this study, pGSN levels were lower in men compared to women. White adults with diabetes had lower levels compared to White adults without diabetes and to African American individuals either with or without diabetes. In addition, pGSN levels were lower in adults with diabetes living below poverty.
Plasma Gelsolin Therapy is a Host-directed Approach to Treating Inflammatory Diseases
Plasma gelsolin (pGSN) is a naturally occurring human protein that is an important component of the innate immune system. As a master regulator of inflammation, its role is to keep inflammation localized to the site of injury and to boost the body’s ability to clear pathogens. Gelsolin can protect organ systems by quelling a potentially over-exuberant inflammatory response and subsequent immune dysregulation by preventing the systemic release of inflammatory mediators.
Normal levels of gelsolin are depleted by diverse inflammatory conditions. Restoring gelsolin levels with the human recombinant form, rhu-pGSN, helps immune cells fight infection and controls inflammation so it does not spread and cause damage. Rhu-pGSN is a non-antibiotic, host-directed treatment for inflammation due to both infectious and non-infectious causes.
BioAegis Therapeutics Inc. is a NJ-based clinical-stage, private company whose mission is to capitalize on a key component of the body’s innate immune system, plasma gelsolin, to prevent adverse outcomes in diseases driven by inflammation and infection.
BioAegis has the exclusive license to broad, worldwide intellectual property through Harvard-Brigham and Women’s Hospital. It holds over 40 patents issued for coverage of inflammatory disease, infection, renal failure, and neurologic disease. BioAegis will also have US biologics exclusivity and has recently filed new IP in areas of unmet need.
1Khatri, N., A. Sagar, N. Peddada, V. Choudhary, B. S. Chopra, V. Garg, R. Garg, and Ashish. 2014. Plasma gelsolin levels decrease in diabetic state and increase upon treatment with F-actin depolymerizing versions of gelsolin. J. Diabetes Res. 2014: 152075.
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