ARA-290 peptide is a 11 amino acid chain derived from the beta domain of protein erythropoietin, a part of the erythropoietin (EPO) considered to assist in tissue regeneration and repair (1). Scientists consider the primary function of the EPO is to stimulate body tissues to produce red blood cells. While the mechanism is not fully understood, EPO is considered by scientists to regulate and optimize the oxygen levels in the body – when the levels are low, more EPO is produced; when the levels are optimal, lesser EPO is produced.
Researchers isolated a small peptide molecule from the EPO protein, called cibinetide, better known as the ARA-290 peptide. Researchers are pivoting their study theses to expand the potential applications of ARA-290 in their research, as the peptide has exhibited versatile potential beyond possible oxygenation and blood cell maintenance.
Scientific findings (4) thus far indicate that once the tissue undergoes an injury, a tissue protective receptor (TPR) pathway is activated. This TPR receptor mainly consists of a beta receptor unit (CD131) along with a subunit from the EPO receptor, jointly called the innate repair receptor. The ARA-290 peptide molecule has been suggested by researchers to bind to this innate repair receptor and possibly attenuate nerve and allodynia-led pain (2). It is also suggested that the ARA-290 peptide may act primarily via this IRR mediated pathway.
Scientists consider that Transient Receptor Potential (TRP) channels may be the primary pain stimulating channels, including possible thermal, chemical, and mechanical stimuli. In the presence of such a causative agent, one of the TRP channels, namely TRPV1, may be triggered. Upon activation, it might induce the ejection of neuropeptides, which then are considered to generate action potential in the nervous systems. This action potential is referred to as “pain” (5). A 2016 study (6) suggested that ARA-290 peptide may have potential as an antagonist to this TRPV1 channel, with researchers further implying that the peptide might inhibit the TRPV1 actions and thereby no neuropeptides will be released to spark a pain response. ARA-290 is still being actively studied for its possible role in pain “mitigation” though researchers have developed hypothesis about its other potential mechanisms of action, including:
- Possible regulation of red blood cell levels
- Possible maintenance of blood vessel function
- May decrease levels of inflammatory cells
- Exhibits potential tissue protective properties
- Exhibits potential immunomodulatory properties
- May mitigate pain levels
Research and Clinical Studies
ARA-290 Peptide and Retinal Ischemia
Recent study (7) has suggested that ARA-290 has the potential to protect the endothelial blood vessels and possibly thereby combat retinal ischemia. A possible mitigation method for retinal ischemia is the restoration of endothelial colonial forming (ECF) cells in the retinal cells. Experimental mice models, induced with retinal ischemia, underwent the ECF cells transplantation for the purpose of this study. To determine the potential of the peptide, the transplantation in some mice occurred in the presence of ARA-290 while the rest was in peptide absence. After the study, it was suggested by the researchers that the peptide exhibited reduction in the inflammatory expression of interleukin cells in the retina.
ARA-290 Peptide and Inflammatory Cytokine Cells
This study (8) was conducted to determine whether the erythropoietin analogue, ARA-290 peptide, also possessed anti-inflammatory and cell protective potential. Pancreatic islet cells are used to regulate blood sugar levels and scientists consider transplantation of damaged pancreatic islet cells with healthy ones to combat diabetes. Scientists note that with such a transplant, often high levels of inflammation accompany the experimental procedure, rendering it ineffective. In this study (8), experimental mice were used, which underwent transplantation surgery for 180+ pancreatic islet cells. The mice were then given ARA-290 peptide right before the surgery and at 0, 6 and 24 hours after surgery. After 12 hours of peptide presence, the liver samples from the mice were collected and analyzed. Peptide cells appeared to exhibit minimal damage of the islets. It was indicated by the researchers that the peptide may have protected the islet cells from cytokines and subsequent apoptosis.
ARA-290 Peptide and Tissue Protection
Based on the research (9) conducted, the ARA-290 peptide is considered to have potential binding capacity with tissue protective receptors (TPR), which may assist maintaining optimal health of the tissues protecting against harmful inflammatory cells and subsequent cellular death. The main potential of ARA-290 peptide over the endogenous erythropoietin cells has been posited by researchers to bind TPR receptor cells, without further cardiovascular or muscular impact (9). This potential of the peptide may help in improving tissue regeneration and reducing tissue morbidity, possibly promoting better wound recovery and healing, and decreasing formation of scars in experimental mouse models.
ARA-290 Peptide and Immunomodulation via TPR Pathway
Scientists posit that the TPR pathway, once stimulated, may express on various immunological cells, including macrophages. With the potential of ARA-290 peptide to bind with the TPR receptor cells, it may restrict the release of certain inflammatory cells such as interleukin IL-6. Owing to a reduced secretion, it may lead to reduced severity of immuno-compromising conditions (9).
ARA-290 Peptide and Immunomodulation via Adaptive Immunity
Research (10) has suggested that ARA-290 peptide may potentially alter the presentation of antigens by the dendritic cells, thereby possibly altering adaptive immunity of the test model. Owing to the peptide’s potential to “fine tune” the antigens, the immune cells may not reject transplanted bodies, potentially leading to successful transplantation experiments in animal models.
ARA-290 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.
1. What is Erythropoietin? Home Health Network. https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/erythropoietin
2. Dahan, A., Dunne, A., Swartjes, M., Proto, P. L., Heij, L., Vogels, O., van Velzen, M., Sarton, E., Niesters, M., Tannemaat, M. R., Cerami, A., & Brines, M. (2013). ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Molecular medicine (Cambridge, Mass.), 19(1), 334–345. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883966/
3. Designation to ARA 290 for the Treatment of Sarcoidosis-associated Small Fiber Neuropathy. https://www.prnewswire.com/news-releases/araim-pharmaceuticals-given-fda-fast-track-designation-to-ara-290-for-the-treatment-of-sarcoidosis-associated-small-fiber-neuropathy-280635872.html
4. Brines M, Cerami A. The receptor that tames the innate immune response. Mol Med. 2012 May 9;18(1):486-96. https://pubmed.ncbi.nlm.nih.gov/22183892/
5. Jara-Oseguera, A., Simon, S. A., & Rosenbaum, T. (2008). TRPV1: on the road to pain relief. Current molecular pharmacology, 1(3), 255–269. https://doi.org/10.2174/1874467210801030255
6. Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides. 2016 Feb;76:73-9. https://pubmed.ncbi.nlm.nih.gov/26774587/
7. O’Leary OE, Canning P, Reid E, Bertelli PM, McKeown S, Brines M, Cerami A, Du X, Xu H, Chen M, Dutton L, Brazil DP, Medina RJ, Stitt AW. The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic. Exp Eye Res. 2019 May;182:144-155. https://pubmed.ncbi.nlm.nih.gov/30876881/
8. Watanabe M, Lundgren T, Saito Y, Cerami A, Brines M, Östenson CG, Kumagai-Braesch M. A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. Transplantation. 2016 Mar;100(3):554-62. https://pubmed.ncbi.nlm.nih.gov/26683514/
9. Peng, B., Kong, G., Yang, C. et al. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell Death Dis 11, 79 (2020). https://doi.org/10.1038/s41419-020-2276-8
10. Yan L, Zhang H, Gao S, Zhu G, Zhu Q, Gu Y, Shao F. EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway. Transplant Proc. 2018 Jun;50(5):1575-1582. https://pubmed.ncbi.nlm.nih.gov/29880388/
11. Nairz, M., Haschka, D., Dichtl, S. et al. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. Sci Rep 7, 13012 (2017). https://doi.org/10.1038/s41598-017-13046-3
12. Bo Huang et al, Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus, published 23 March 2018. https://doi.org/10.1111/jcmm.13608
NOTE: These products are intended for laboratory research use only. ARA-290 for sale (16mg) is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.