ARA-290

Wang RL, Yang ZH, Huang YY, Hu Y, Wang YL, Yan F, et al.

CNS neuroscience & therapeutics

In a mouse middle cerebral artery occlusion (ischemic stroke) model, ARA-290 reduced neuronal apoptosis and inflammatory cytokine levels in brain tissue; silencing the beta-common receptor (CD131) with siRNA suppressed this effect, localizing the peptide's action to beta-common-receptor-dependent signaling distinct from the erythropoiesis-driving EPO receptor homodimer pathway.

Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, Ashari S, Ghiabi S, Bayrami Z

Inflammation

In cisplatin-exposed HEK-293 and ACHN kidney cell lines, ARA-290 pre-exposure lowered markers of DNA damage, oxidative stress (ROS, MDA) and pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta), and shifted apoptosis-pathway gene/protein expression (lower caspase-3 and Bax, higher Bcl-2) relative to cisplatin alone, consistent with an anti-apoptotic, antioxidant mechanism in this in vitro nephrotoxicity model.

Dennhardt S, Pirschel W, Wissuwa B, Imhof D, Daniel C, Kielstein JT, et al.

Frontiers in immunology

In a Shiga toxin-induced hemolytic-uremic syndrome model in mice, administration of erythropoietin or its non-hematopoietic analog pHBSP (the ARA-290 peptide) via the EPO receptor/innate-repair-receptor axis improved 7-day survival and reduced renal oxidative stress in the murine model; pHBSP specifically (but not EPO) also attenuated renal nitrosative stress, without thromboembolic complications, though renal dysfunction/injury markers were not significantly reduced.

Awida Z, Bachar A, Saed H, Gorodov A, Ben-Califa N, Ibrahim M, et al.

International journal of molecular sciences

In C57BL/6J mice, one month of cibinetide (the ARA-290 peptide) treatment alone increased cortical (~5.8%) and trabecular (~5.2%) bone mineral density; when co-administered with EPO, cibinetide reduced circulating osteoclast progenitor numbers by 42.8% versus EPO alone, and in parallel in vitro assays cibinetide (alone or with EPO) inhibited osteoclast differentiation from precursor cells — indicating the EPO receptor/CD131 heteroreceptor pathway this non-erythropoietic analog engages modulates osteoclast biology independent of hematopoietic EPO signaling.

Brines M, Patel NS, Villa P, Brines C, Mennini T, De Paola M, et al.

Proceedings of the National Academy of Sciences of the United States of America

This foundational study delimited EPO's tissue-protective activity to helix B (residues 58-82) and further to an 11-amino-acid peptide (the design later developed as ARA-290/cibinetide) that reproduced tissue-protective effects in rodent models of ischemic stroke, renal ischemia-reperfusion, wound healing, and cognitive-performance assays, while showing no erythropoietic activity in vitro or in vivo.