Immunomodulatory and Kidney-Protective Effects of the Human Chorionic Gonadotropin Derivate EA-230

Abstract

The systemic inflammatory response following infectious or non-infectious insults is related to morbidity (including acute kidney injury) and mortality. Pregnancy is associated with immunotolerance and an increased glomerular filtration rate. EA-230, a linear tetrapeptide (Alanine-Glutamine-Glycine-Valine), derived from the β-chain of the human chorionic gonadotropin hormone, has shown immunomodulatory and renoprotective properties in several pre-clinical animal models of systemic inflammation. Furthermore, an excellent safety profile of EA-230 was observed in phase 1 studies in humans, and the immunomodulatory effects of EA-230 were recently demonstrated in a phase IIa study during human experimental endotoxemia. A prospective double-blind placebo-controlled randomized trial in 180 patients undergoing elective CABG-surgery with or without valve surgery is currently conducted to investigate the immunomodulatory and renoprotective properties of EA-230.

Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study

“…In the latter, surgical damage and stress result in the release of a multitude of danger-associated molecular patterns, ischemia-reperfusion injury, hemorrhagic shock, and possibly translocation of (components of) microorganisms from the gut to the circulation ( 3 , 17 – 19 ). Nevertheless, previous animal studies have demonstrated immunomodulatory effects of EA-230 in various types of inflammation, including models of ischemia-reperfusion injury ( 34 – 36 ), and hemorrhagic shock ( 31 ). These models recapitulate distinct aspects of the inflammatory response observed following cardiac surgery and therefore may render this explanation for the absence of immunomodulatory effects in the current study less plausible.…”

“…Treatment with EA-230 attenuated pro-inflammatory cytokine release, prevented organ dysfunction and renal injury, and improved survival in several animal models of systemic inflammation (27)(28)(29)(30)(31)(32)(33). Furthermore, EA-230 mitigated renal injury and improved survival in murine models of renal transplantation and renal ischemia-reperfusion injury (34)(35)(36). Finally, EA-230 was shown to be well tolerated in phase 1 studies (37) and attenuated the release of inflammatory mediators during experimental human endotoxemia (38).…”

Review: Lessons Learned From Clinical Trials Using Antimicrobial Peptides (AMPs)

“…The latter has been pursued by several companies. The AMPs OP-145 ( Nell et al, 2006 ), P113 ( Woong et al, 2008 ), LTX-109 ( Midura-Nowaczek and Markowska, 2014 ), and EA-230 ( Van Groenendael et al, 2018 ) all consist of a lower number of amino acids as compared to their “original” peptide LL-37, histatin-5, bovine lactoferrin and loop-2 of β-hCG, respectively. Beside truncation of AMPs, the synthesis of ultra-short AMPs such as the 5-amino acid linear peptide SGX942 further reduces the production costs of AMPs ( Kudrimoti et al, 2016 ).…”