GENEMEDICS APP

GENEMEDICS NUTRITION

HEALTH LIBRARY

ARA 290

ARA 290, also known as cibinetide, is an 11–amino acid peptide that has potent tissue-protective and tissue-regenerative properties. It is called “nonhematopoietic peptide” because ARA 290 exerts its beneficial effects without stimulating erythropoesis or red blood cell production. Preclinical and clinical studies have shown that by selectively interacting with the innate repair receptor, ARA 290 mediates tissue protection.

Overall Health Benefits of ARA 290

  • Relieves neuropathic pain [1-19]
  • Fights diabetes [2] [19-26]
  • Promotes tissue repair [5] [27-37]
  • Boosts immune function [38-45]

Proven Health Benefits of ARA 290

Relieves Neuropathic Pain

Neuropathic pain is often debilitating because it presents as a shooting or burning pain. Sometimes, it can resolve on its own but is usually chronic in nature. In worst cases, it comes and goes and can significantly alter one’s quality of life. Interestingly, there is an overwhelming body of clinical evidence suggesting that ARA 290 can offer long-term relief for neuropathic pain associated with nerve damage or a malfunctioning nervous system:

  • A 2016 study published in the Peptides journal found that ARA 290-mediated analgesic effect is achieved by blocking or influencing receptors in pain sensation. [1]
  • In patients with type 2 diabetes who are suffering from neuropathic symptoms, ARA 290 showed significant potential for the treatment of diabetic small fiber neuropathy. [2]
  • In patients with neuropatchic pain related to sarcoidosis, an inflammatory disease affecting multiple body organs, ARA 290 significantly reduced pain and improved quality of life. [3-8]
  • A 2016 study published in the Pain Reports journal found that ARA 290 treats neuropathic pain by effectively reprograming the pro-inflammatory and tissue-damaging process into healing and tissue repair. [9]
  • In a rat neuritis (nerve inflammation) model, ARA 290 prevented the development of mechanical allodynia (increased pain sensitivity to non-painful stimuli). [10]
  • In a mouse model of diabetic neuropathy, ARA 290 induced repair of small autonomic nerve fibers within the sympathetic ganglia (nerve cell bodies along the spinal cord). [11]
  • In mice with pain associated with sciatic nerve injury, ARA 290 prevented the development of mechanical allodynia. [12]
  • In rats, weekly injections with ARA 290 produced long-term relief of neuropathic pain. [13]
  • In mice with spinal cord injury, ARA 290 reduced neuropathic pain by suppressing spinal inflammatory mediators such as CCL2. [14]
  • In a murine model, ARA 290 reduced neuropathic pain by reducing the levels of the inflammatory substance TNF-α. [15]
  • In mice, ARA 290 relieved capsaicin-induced mechanical allodynia by inhibiting capsaicin-evoked TRPV1 channel activity, a modulator of nerve inflammation and pain sensation. [16]
  • Studies found that ARA 290 relieves neuropathic pain in patients with sarcoidosis by improving corneal nerve fiber abundance. [17-18]

Fights Diabetes

Evidence also suggests that ARA 290 possesses potent anti-diabetic properties that can be beneficial in patients with diabetes mellitus and chronically elevated blood sugar levels:

  • In patients with type 2 diabetes, ARA 290 administration at a dose of 4 mg daily for 28 days resulted in a significant improvement in hemoglobin A1c. [2]
  • In diabetic patients, ARA 290 administration restored glucose homeostasis (blood sugar balance). [19]
  • A study found that ARA 290 promotes glucose homeostasis by targeting the innate repair receptor. [20]
  • In individuals with prediabetes and/or drug-naive type 2 diabetes, ARA 290 administration resulted in improved glucose tolerance, insulin secretion, insulin sensitivity and long-term glucose control. [21]
  • In type 2 diabetic Goto-Kakizaki (GK) rats, oral administration of ARA 290 for 4 weeks improved β-cell glucose metabolism and [Ca(2+)]i handling, resulting in enhanced insulin release. [22-23]
  • In animal models of diabetic neuropathy, ARA 290 improved blood sugar levels by reducing the underlying inflammation. [7]
  • In a murine model, ARA 290 reversed diabetes-induced autonomic nerve degeneration. [24]
  • In patients with prediabetes and type 2 diabetes, ARA 290 treatment for 2-4 weeks improved oral glucose tolerance tests and insulin secretion. [25]
  • In rats, ARA 290 protected pancreatic islets (secretes insulin) from cytokine-induced damage and programmed cell death (apoptosis). [26]

Promotes Tissue Repair

By selectively interacting with the innate repair receptor, ARA 290 exerts its regenerative effects on different body tissues. Strong scientific evidence supports its benefits on various forms of tissue injuries:

  • In animal models of kidney injury associated with lack of blood (ischemia), intravenous injection of ARA 290 improved kidney function and reduced structural damage. [27-28]
  • In mice with deep partial thickness cutaneous burn injury, ARA 290 mitigated the innate inflammatory response and decreased the burn depth area. [29]
  • In mice, ARA 290 administration protected against rhabdomyolysis-induced acute kidney injury. [30]
  • A 2018 mice study published in the Journal of Cellular and Molecular Medicine also found that ARA 290 prevents programmed cell death (apoptosis) of kidney cells. [31]
  • In a rat model of inflammatory pain, ARA 290 induced regeneration of nerve fibers. [32]
  • In mice, ARA 290 protected islets of the pancreas from cytokine-induced damage and apoptosis. [33]
  • In rats, ARA 290 protected against early renal allograft injury (tissue damage associated with kidney transplant) by reducing macrophage infiltration. [34]
  • In patients with sarcoidosis-associated small nerve fiber loss, ARA 290 stimulated eye tissue repair by increasing corneal nerve fiber density. [5]
  • A 2009 study published in the Journal of Molecular Medicine found that nonerythropoietic tissue protective compounds such as ARA 290 are highly effective facilitators of wound healing. [35]
  • In rats with spinal cord injury, ARA 290 treatment resulted in an increased activity of the cells of the spinal cord. [7]
  • In rats with nerve inflammation, ARA 290 treatment suppressed inflammation and exhibited tissue protection. [36]
  • In mouse cells, ARA 290 restored tissue homeostasis by modulating pro-inflammatory signaling pathways.[37]

Boosts Immune Function

A growing body of evidence suggests that ARA 290 also has immune-modulating properties necessary for warding off a wide array of diseases:

  • In a cell culture model, ARA 290 modulated the innate immune response and reduced invasion of the bacterium Escherichia coli. [38]
  • Several studies also found that ARA 290 and other nonhematopoietic peptides have the potential to combat several inflammatory and infectious diseases. [39-41]
  • A 2017 study published in Scientific Reports found that ARA 290 enhances immune cell function through its potent anti-inflammatory effects. [42]
  • A 2016 study found that ARA 290 improves stem cells’ ability to find their destination (homing), thus, enhancing new blood vessel formation, tissue regeneration, and immune function. [43]
  • A 2014 study published in the Journal of Immunology found that ARA 290 alters T cell function to suppress inflammation. [44]
  • A study found that ARA 290 can help lower the risk of myocardial infarction by protecting against damage to the heart muscle (myocardium). [45]

References:

    1. Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides. 2016;76:73-9.
    2. Brines M, Dunne AN, Van velzen M, et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med. 2015;20:658-66.
    3. Heij L, Niesters M, Swartjes M, et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med. 2012;18:1430-6.
    4. Available from https://www.tandfonline.com/doi/full/10.1517/21678707.2013.719289.
    5. Dahan A, Dunne A, Swartjes M, Proto PL, Heij L, Vogels O, van Velzen M, Sarton E, Niesters M, Tannemaat MR, Cerami A, Brines M. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med 2013;19:334–45.
    6. Niesters M, Swartjes M, Heij L, Brines M, Cerami A, Dunne A, Hoitsma E, Dahan A. The erythropoietin analog ARA 290 for treatment of sarcoidosis-induced chronic neuropathic pain. Expert Opin Orphan Drugs 2013;1:77–87.
    7. Swartjes M, van Velzen M, Niesters M, Aarts L, Brines M, Dunne A, Cerami A, Dahan A. ARA 290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response. Mol Pain 2014;10:13.
    8. van Velzen M, Heij L, Niesters M, Cerami A, Dunne A, Dahan A, Brines M. ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig Drugs 2014;23:541–50.
    9. Dahan A, Brines M, Niesters M, Cerami A, van Velzen M. Targeting the innate repair receptor to treat neuropathy. Pain Rep. 2016;1(1):e566. Published 2016 Aug 9. doi:10.1097/PR9.0000000000000566.
    10. Pulman KG, Smith M, Mengozzi M, Ghezzi P, Dilley A. The erythropoietin-derived peptide ARA290 reverses mechanical allodynia in the neuritis model. Neuroscience 2013;233:174–83.
    11. Schmidt RE, Feng D, Wang Q, Green KG, Snipes LL, Yamin M, Brines M. Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia. Exp Neurol 2011;232:126–35.
    12. Pulman KG, Smith M, Mengozzi M, Ghezzi P, Dilley A. The erythropoietin-derived peptide ARA290 reverses mechanical allodynia in the neuritis model. Neuroscience 2013;233:174–83.
    13. Swartjes M, Morariu A, Niesters M, Brines M, Cerami A, Aarts L, Dahan A. ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain: an experimental study in rats and beta-common receptor knockout mice. Anesthesiology 2011;115:1084–92.
    14. Swartjes M, Niesters M, Heij L, Dunne A, Aarts L, Hand CC, Kim HS, Brines M, Cerami A, Dahan A. Ketamine does not produce relief of neuropathic pain in mice lacking the beta-common receptor (CD131). PLoS One 2013;8:e71326.
    15. Takahashi T, Kinoshita M, Shono S, Habu Y, Ogura T, Seki S, Kazama T. The effect of ketamine anesthesia on the immune function of mice with postoperative septicemia. Anesth Analgesia 2010;111:1051–8.
    16. Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides 2016;76:73–9.
    17. Culver DA, Dahan A, Bajorunas D, et al. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain. Invest Ophthalmol Vis Sci. 2017;58(6):BIO52-BIO60.
    18. Retrieved from https://clinicaltrials.gov/ct2/show/NCT02039687.
    19. Retrieved from https://pdfs.semanticscholar.org/7d4b/9ec022053c196726a65c4fe1732736d6aa48.pdf
    20. Retrieved from https://doloranimal.org/images/fdocum/

targeting_the_innate_repair_receptor_to_treat.2.pdf

  • Retrieved from https://ichgcp.net/clinical-trials-registry/NCT01933529
  • Muller C, Yassin K, Li LS, et al. ARA290 Improves Insulin Release and Glucose Tolerance in Type 2 Diabetic Goto-Kakizaki Rats. Mol Med. 2016;21(1):969–978. doi:10.2119/molmed.2015.00267.
  • Muller C, et al. (2013) The nonhematopoietic erythropoietin analogue ARA 290 improves glucose tolerance by stimulating insulin secretion in spontaneously type 2 diabetic Goto-Kakizaki rats. Diabetologia. 56(Suppl 1):S268.
  • Schmidt RE, et al. Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia. Exp Neurol. 2011;232:126–35.
  • Retrieved from https://clinicaltrials.gov/ct2/show/NCT01933529
  • Available from https://www.researchgate.net/publication/310146980_An_Engineered_Innate_Repair_Receptor_Agonist_ARA_290_Protects_Rat_Islets_from_Cytokine-induced_Apoptosis.
  • Van rijt WG, Nieuwenhuijs-moeke GJ, Van goor H, et al. ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury. J Transl Med. 2013;11:9.
  • Van rijt WG, Nieuwenhuijs-moeke GJ, Van goor H, Ottens PJ, Ploeg RJ, Leuvenink HG. Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury. J Transl Med. 2013;11:286.
  • Bohr S, Patel SJ, Shen K, et al. Alternative erythropoietin-mediated signaling prevents secondary microvascular thrombosis and inflammation within cutaneous burns. Proc Natl Acad Sci USA. 2013;110(9):3513-8.
  • Retrieved https://www.nature.com/articles/cddis2017104
  • Huang B, Jiang J, Luo B, et al. Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus. J Cell Mol Med. 2018;22(7):3330-3339.
  • Dilley A. ARA290 in a rat model of inflammatory pain. Methods Mol Biol. 2013;982:213-25.
  • Watanabe M, Lundgren T, Saito Y, et al. A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. Transplantation.2016;100(3):554-62.
  • Yan L, Zhang H, Gao S, et al. EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway. Transplant Proc. 2018;50(5):1575-1582.
  • Erbayraktar Z, Erbayraktar S, Yilmaz O, Cerami A, Coleman T, Brines M. Nonerythropoietic tissue protective compounds are highly effective facilitators of wound healing. Mol Med. 2009;15(7-8):235–241. doi:10.2119/molmed.2009.00051.
  • Liu Y, Luo B, Han F, et al. Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection [published correction appears in PLoS One. 2014;9(5):e99555. Dosage error in article text]. PLoS One. 2014;9(3):e90942. Published 2014 Mar 6. doi:10.1371/journal.pone.0090942.
  • Bohr S, Patel SJ, Vasko R, et al. Modulation of cellular stress response via the erythropoietin/CD131 heteroreceptor complex in mouse mesenchymal-derived cells. J Mol Med (Berl). 2015;93(2):199–210. doi:10.1007/s00109-014-1218-2.
  • Polgárová K, Lüthje P, Cerami A, Brauner A. The erythropoietin analogue ARA290 modulates the innate immune response and reduces Escherichia coli invasion into urothelial cells. FEMS Immunol Med Microbiol. 2011;62(2):190-6.
  • Macdougall I.C., Rossert J., Casadevall N., Stead R.B., Duliege A.M., Froissart M., Eckardt K.U. A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia. N. Engl. J. Med. 2009;361:1848–1855.
  • Wrighton N.C., Farrell F.X., Chang R., Kashyap A.K., Barbone F.P., Mulcahy L.S., Johnson D.L., Barrett R.W., Jolliffe L.K., Dower W.J. Small peptides as potent mimetics of the protein hormone erythropoietin. Science. 1996;273:458–464.
  • Brines M., Patel N.S., Villa P., Brines C., Mennini T., De Paola M., Erbayraktar Z., Erbayraktar S., Sepodes B., Thiemermann C., Ghezzi P., Yamin M., Hand C.C., Xie Q.W., Coleman T., Cerami A. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc. Natl. Acad. Sci. U S A. 2008;105:10925–10930.
  • Nairz M, Haschka D, Dichtl S, et al. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. Sci Rep. 2017;7(1):13012.
  • Hache G, Garrigue P, Bennis Y, et al. ARA290, a Specific Agonist of Erythropoietin/CD131 Heteroreceptor, Improves Circulating Endothelial Progenitors’ Angiogenic Potential and Homing Ability. Shock. 2016;46(4):390-7.
  • Chen H, Luo B, Yang X, et al. Therapeutic effects of nonerythropoietic erythropoietin analog ARA290 in experimental autoimmune encephalomyelitis rat. J Neuroimmunol. 2014;268(1-2):64-70.
  • Ahmet I, et al. A small nonerythropoietic helix B surface peptide based upon erythropoietin structure is cardioprotective against ischemic myocardial damage. Mol Med. 2011;17:194–200.

 

testimonial
before after

At the age of 60, I look and feel better than I ever have in my entire life! Switching my health program and hormone replacement therapy regimen over to Genemedics was one of the best decisions I’ve ever made in my life! Genemedics and Dr George have significantly improved my quality of life and also dramatically improved my overall health. I hav...

- Nick Cassavetes, 60 yrs old

Movie Director (“The Notebook”, “John Q”, “Alpha Dog”), Actor and Writer

Call 800-277-4041 for a Free Consultation

What to expect during your consultation:
  • Usually takes 15-30 minutes
  • Completely confidential
  • No obligation to purchase anything
  • We will discuss your symptoms along with your health and fitness goals
  • Free post-consult access for any additional questions you may have
Contact Us Page
Sending

Genemedics® Health Institute is a global premier institute dedicated to revolutionizing health and medicine through healthy lifestyle education, guidance and accountability in harmony with functional medicine. Our physician-supervised health programs are personally customized to help you reach your health and fitness goals while looking and feeling better than ever.