ARA-290 10mg

ARA-290 is a derivative of erythropoietin that reduces inflammation by activating innate repair receptors. It has shown benefits in lowering blood sugar (HbA1c), improving cholesterol levels, alleviating neuropathic pain, and promoting wound healing. Support your body’s repair systems naturally with ARA-290. Order now and enhance your inflammatory balance and heaARA-290, also known as Cibinetide, is a synthetic peptide derived from a segment of the erythropoietin (EPO) hormone. Unlike EPO, ARA-290 does not stimulate red blood cell production but retains EPO's tissue-protective and anti-inflammatory properties. It selectively activates the innate repair receptor (IRR), a complex of the EPO receptor (EPOR) and β common receptor (βcR), triggering signaling pathways that promote tissue repair and modulate inflammation. 

ARA-290 Research

ARA-290 and Blood Vessel Health

Retinal ischemia, a major cause of blindness, results from various diseases damaging the retinal epithelial cells. Research in mice shows that ARA-290 protects endothelial colony forming cells (ECFCs) from inflammation-induced damage, enhancing their survival and ability to repair blood vessels. Additionally, ARA-290 promotes the growth, movement, and lifespan of ECFCs across the vascular system. It also improves their targeting to damaged blood vessels, which may boost the success of transplanted ECFC therapies aimed at restoring blood flow to ischemic tissues. If successful, this could revolutionize cell transplantation therapies for tissue repair and more.

Reducing Inflammatory Cytokines

ARA-290 helps prolong the survival of transplanted insulin-producing islet cells by suppressing macrophage activation and reducing harmful inflammatory cytokines such as IL-6, IL-12, and TNF-alpha. Since islet transplantation has been limited by poor cell survival, ARA-290’s ability to modulate inflammation offers hope to improve this therapy. This peptide works by binding to the tissue-protective receptor (TPR), enhancing tissue defense and immune regulation without triggering the cardiovascular side effects commonly seen with erythropoietin (EPO), which also binds this receptor. The overall outcome includes reduced cell death, improved tissue healing, faster recovery, and less scarring.

Immune System Modulation

The TPR is present on various immune cells including macrophages, dendritic cells, mast cells, and lymphocytes. ARA-290’s binding to TPR on these cells directly influences immune responses. In macrophages, TPR activation by ARA-290 decreases secretion of pro-inflammatory cytokines like TNF-alpha and IL-6. Although this can reduce pathogen clearance in some situations, it lessens disease severity and prevents chronic inflammation. Furthermore, TPR activation limits macrophage chemokine release, reducing harmful inflammation while promoting tissue macrophage recruitment to injury sites, facilitating improved healing.

ARA-290 also impacts dendritic cells by modifying antigen presentation, which can adjust adaptive immune responses. This is significant because adaptive immunity plays a major role in transplant rejection. Modulating this process may help reduce graft rejection in organ and bone marrow transplants.

Potential Applications in Autoimmune and Inflammatory Diseases

ARA-290 shows promise in treating inflammatory bowel disease such as Crohn’s disease and ulcerative colitis by offering a more targeted immune modulation approach than current injectable treatments. It may also help manage systemic lupus erythematosus (SLE) by reducing disease markers (autoantibodies) and protecting kidneys from damage, potentially offering a novel targeted therapy.

Pain Perception and Neuropathy

The immune system influences pain perception, especially neuropathic pain common in diabetes and other conditions. ARA-290 acts on the innate repair receptor (IRR) and may also inhibit TRPV1 channels responsible for heat and burning sensations in neuropathic pain. This dual action makes it a candidate for treating pain associated with diabetes, multiple sclerosis, chemotherapy, and amputations.

ARA-290 has demonstrated the ability to increase small nerve fiber density and reduce pain in conditions like small fiber neuropathy—a debilitating nerve damage seen in diseases such as sarcoidosis, diabetes, and HIV.

Orphan Drug Status and Clinical Trials

In 2016, ARA-290 (also known as cibinetide) was granted orphan drug status by the FDA for treating painful sarcoid neuropathy. Clinical research led by Dr. Michael Brines showed promising results in reducing peripheral nerve pain and improving nerve function. Phase 3 trials are underway for diabetic and sarcoid neuropathy, aiming to address nerve damage in millions of affected patients. Early studies also suggest ARA-290 may enhance wound healing in diabetic models, potentially reducing the need for amputations and chronic ulcer management.

Summary

ARA-290 is primarily recognized for its novel ability to control neuropathic pain but also has significant immune-modulating and tissue-protective properties. It supports wound repair and protects blood vessels during ischemic injury. Ongoing clinical trials are exploring its potential to treat a range of neuropathies, systemic lupus erythematosus, inflammatory bowel disease, and pain syndromes related to multiple sclerosis, HIV, and more.

ARA-290 exhibits minimal side effects with good bioavailability in mice; however, mouse dosing does not directly translate to humans. It is sold for research purposes only and should be purchased exclusively by licensed researchers.

Research Applications

ARA-290 is primarily utilized in scientific studies focusing on:

• Neuropathy: Investigating its potential to alleviate neuropathic pain associated with conditions like diabetic neuropathy and sarcoidosis.
• Tissue Repair: Exploring its role in promoting wound healing and tissue regeneration in various injury models.
• Inflammation Modulation: Studying its effects on reducing inflammation in autoimmune diseases and other inflammatory conditions.
• Neuroprotection: Assessing its potential in protecting nerve cells from damage in neurological disorders.

Product Specifications

• Form: Lyophilized (freeze-dried) powder for reconstitution.
• Dosage: Each vial contains 10mg of ARA-290.
• Purity: Typically ≥99%, ensuring high-quality material for research purposes.
• Packaging: Available in sealed vials containing 10mg of ARA-290 powder.
• Storage: Store lyophilized ARA-290 at temperatures below -18°C. After reconstitution, store at 4°C and use within 2-7 days.

Safety and Handling

ARA-290 is intended strictly for laboratory research and is not approved for human consumption. Handle with care, following appropriate safety protocols. Ensure proper storage conditions to maintain the integrity and efficacy of the compound.

Referenced Citations

• M.S. Hosseini-Zare, S. Dashti-Khavidaki, M. Mahdavi-Mazdeh, F. Ahmadi, and S. Akrami, "Peripheral neuropathy response to erythropoietin in type 2 diabetic patients with mild to moderate renal failure," Clinical Neurology and Neurosurgery, vol. 114, no. 6, pp. 663–667, July 2012. doi: 10.1016/j.clineuro.2012.01.007.
• E. O'Leary et al., "The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic," Experimental Eye Research, vol. 182, pp. 144–155, 2019. doi: 10.1016/j.exer.2019.03.001.
• G. Hache et al., "ARA-290, a specific agonist of erythropoietin/CD131 heteroreceptor, improves circulating endothelial progenitors’ angiogenic potential and homing ability," Shock, vol. 46, no. 4, pp. 390–397, 2016. doi: 10.1097/SHK.0000000000000606.
• M. Watanabe et al., "A non-hematopoietic erythropoietin analogue, ARA-290, inhibits macrophage activation and prevents damage to transplanted islets," Transplantation, vol. 100, no. 3, pp. 554–562, March 2016. doi: 10.1097/TP.0000000000001026.
• B. Peng, G. Kong, C. Yang, and Y. Ming, "Erythropoietin and its derivatives: from tissue protection to immune regulation," Cell Death & Disease, vol. 11, no. 2, p. 79, Feb. 2020. doi: 10.1038/s41419-020-2276-8.
• L. Yan et al., "EPO derivative ARA-290 attenuates early renal allograft injury in rats by targeting NF-κB pathway," Transplantation Proceedings, vol. 50, no. 5, pp. 1575–1582, 2018. doi: 10.1016/j.transproceed.2018.03.015.
• M. Nairz et al., "Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis," Scientific Reports, vol. 7, no. 1, p. 13012, Dec. 2017. doi: 10.1038/s41598-017-13046-3.
• B. Huang et al., "Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus," Journal of Cellular and Molecular Medicine, vol. 22, no. 7, pp. 3330–3339, 2018. doi: 10.1111/jcmm.13606.
• M. Brines et al., "ARA-290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes," Molecular Medicine, vol. 20, pp. 656–666, March 2015. doi: 10.2119/molmed.2014.00215.
• D.A. Culver et al., "Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain," Investigative Ophthalmology & Visual Science, vol. 58, no. 6, pp. BIO52–BIO60, 2017. doi: 10.1167/iovs.16-21291.
• M. van Velzen et al., "ARA-290 for treatment of small fiber neuropathy in sarcoidosis," Expert Opinion on Investigational Drugs, vol. 23, no. 4, pp. 541–550, April 2014. doi: 10.1517/13543784.2014.892072.
• A. Bitto et al., "Activation of the EPOR-common receptor complex by cibinetide ameliorates impaired wound healing in mice with genetic diabetes," Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1864, no. 2, pp. 632–639, Feb. 2018. doi: 10.1016/j.bbadis.2017.12.006.