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    Neuropeptides•Updated 2026-03-13•7 min read

    What Is ARA-290? Benefits, Research & Safety

    An 11-amino-acid peptide derived from erythropoietin (EPO) that selectively activates the innate repair receptor (IRR) without stimulating red blood cell production, researched for neuroprotection, tissue repair, and anti-inflammatory effects.

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    Also known as:
    Cibinetide
    ARA 290
    EPO-derived peptide
    CLimited human evidenceUK: Unlicensed (UK)WADA: Sport status unclear

    UK summary: Investigational peptide derived from EPO (innate-repair-receptor agonist; lacks EPO's erythropoietic activity). Studied for small-fibre neuropathy and sarcoidosis-related pain; not currently a licensed UK medicine.

    Quick Facts

    Category
    Neuropeptides
    Half-Life
    Approximately 10–15 minutes (short plasma half-life, but biological effects persist for hours due to sustained intracellular signalling following receptor activation)
    UK Status
    Investigational compound. Not licensed by the MHRA for any therapeutic indication.
    EU Status
    Not authorised by the EMA. Has received orphan medicinal product designation for sarcoidosis in the EU.

    Overview

    ARA-290, also known by its International Nonproprietary Name cibinetide, is a synthetic 11-amino-acid linear peptide engineered to replicate the tissue-protective signalling of erythropoietin (EPO) without its haematopoietic (blood cell-stimulating) effects. Developed by Araim Pharmaceuticals, ARA-290 selectively activates the innate repair receptor (IRR), a heteromeric receptor complex composed of the EPO receptor (EPOR) and the beta common receptor (βcR/CD131). The critical innovation of ARA-290 lies in its ability to decouple EPO's protective functions from its blood-thickening effects. Native EPO, while powerfully tissue-protective, stimulates erythropoiesis (red blood cell production), which can lead to dangerous increases in blood viscosity, thrombosis risk, and cardiovascular complications — particularly problematic for patients who might benefit from tissue protection but cannot tolerate haematological effects. ARA-290 has been investigated in multiple clinical trials for conditions including sarcoidosis-related small fibre neuropathy, diabetic neuropathy, chronic pain syndromes, and various inflammatory conditions. Its unique mechanism positions it at the intersection of neuroprotection, immune modulation, and tissue repair. ARA-290/cibinetide has undergone clinical trials but is not yet approved for therapeutic use by any major regulatory authority. All information presented here is for educational purposes based on published research.
    Evidence standards summary

    ARA-290 — evidence and risk at a glance

    Twenty standard modules scored against the Peptide Authority evidence grading methodology. Missing modules indicate the field has not yet been characterised editorially — treat absences as uncertainty rather than reassurance.

    01Evidence snapshot

    CLimited human evidenceOverall grade against our evidence grading methodology.

    Investigational peptide derived from EPO (innate-repair-receptor agonist; lacks EPO's erythropoietic activity). Studied for small-fibre neuropathy and sarcoidosis-related pain; not currently a licensed UK medicine.

    02Human evidence grade

    CLimited human evidenceStrength of evidence from published human trials.

    03Preclinical evidence grade

    BModerate human evidenceAnimal-model and in-vitro evidence quality.

    04Regulatory status

    • UK: Investigational compound. Not licensed by the MHRA for any therapeutic indication.
    • EU: Not authorised by the EMA. Has received orphan medicinal product designation for sarcoidosis in the EU.
    • Notes: ARA-290 (cibinetide) has been evaluated in multiple clinical trials and received orphan drug designation for sarcoidosis. Despite promising Phase II results, it has not yet achieved regulatory approval from any major authority. It is not available as a research chemical in the same manner as many research peptides — access has been primarily through clinical trial participation.

    05Approved medical uses

    None in the UK or EU as a finished medicine. (Or: not yet documented; treat as absence rather than approval.)

    06Unapproved / promotional claims

    • Cures neuropathy.
    • Available for UK private prescription.

    07Common internet claims

    • Marketed by some chronic-pain communities ahead of licensing.

    08Claim vs evidence

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Approved for neuropathy”ENoHighARA-290 is investigational with some encouraging Phase 2 data; not approved for any indication.

    09Safety uncertainty score

    Moderate

    Safety profile partly characterised; some signals from observational or preclinical data.

    10Known adverse signals

    • Phase 2 trial profile: generally well tolerated short-term.
    • Lacks EPO's erythropoietic activity (designed advantage).
    • Long-term safety beyond trial timeframes unstudied.

    11Drug-interaction uncertainty

    Moderate

    Some interaction data published; check with a prescriber for your specific medicines.

    12Anti-doping status

    WADA: Sport status unclearWADA strict-liability framing applies.

    13UK legal position

    UK: Unlicensed (UK)

    Investigational compound. Not licensed by the MHRA for any therapeutic indication.

    Read the full UK legal guide → Research peptides and UK law

    14EU legal position

    Not authorised by the EMA. Has received orphan medicinal product designation for sarcoidosis in the EU.

    15What this page cannot tell you

    • Whether grey-market 'ARA-290' contains the labelled compound.
    • Whether Phase 3 will confirm Phase 2 neuropathy signal.

    16Last reviewed

    Last reviewed:

    Next review due:

    Spotted an error or something out of date? Send a correction.

    17Citation quality score

    BModerate human evidenceQuality of the sources we cite, graded against the evidence grading methodology.

    18Research gaps

    • Phase 3 not completed; UK regulatory submission not active.

    19Safer alternatives / established care pathways

    • NICE NG193 / CG173 neuropathic pain pathway via NHS.
    • Clinical trial enrolment via ClinicalTrials.gov for genuinely refractory cases.

    Related Safety Centre page → Unlicensed peptide risks

    20Doctor discussion prompts

    Questions to ask a qualified clinician

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Are there UK trials of ARA-290 for my situation?
    • What licensed neuropathy treatments should I consider?

    Discovery & History

    The development of ARA-290 arose from pioneering research into the non-haematopoietic tissue-protective functions of erythropoietin, led by Professor Anthony Cerami and Dr. Michael Brines at the Kenneth S. Warren Institute and subsequently Araim Pharmaceuticals. In the early 2000s, research demonstrated that EPO possessed potent tissue-protective properties independent of its well-known role in stimulating red blood cell production. Studies showed that EPO could protect neurons, cardiomyocytes, and other tissues from ischaemic, toxic, and inflammatory damage. However, the clinical application of EPO for tissue protection was severely limited by its haematopoietic effects — chronic EPO administration increased haematocrit, blood viscosity, and thromboembolic risk. Brines and Cerami identified that EPO's tissue-protective effects were mediated through a distinct receptor complex — the innate repair receptor (IRR) — rather than the classical homodimeric EPO receptor responsible for erythropoiesis. This discovery opened the possibility of designing molecules that selectively activated the IRR without stimulating red blood cell production. Through systematic structure–activity studies, the team identified the specific regions of the EPO molecule responsible for IRR binding and engineered a minimal peptide — ARA-290 — that retained tissue-protective activity whilst lacking erythropoietic stimulation. The 11-amino-acid sequence was optimised for receptor binding, stability, and manufacturability. ARA-290 entered clinical trials in the 2010s, with studies in sarcoidosis, diabetic neuropathy, and other neuropathic conditions. Results demonstrated meaningful improvements in small fibre nerve density and neuropathic symptoms, representing a novel therapeutic approach to conditions with limited treatment options.

    Mechanism of Action

    ARA-290 acts through a highly specific receptor-mediated mechanism that engages endogenous tissue repair and anti-inflammatory pathways: **Innate Repair Receptor (IRR) Activation** ARA-290 selectively binds to and activates the innate repair receptor, a heteromeric complex consisting of the erythropoietin receptor (EPOR) and the beta common receptor (βcR/CD131). The IRR is expressed on a wide range of cell types including neurons, Schwann cells, endothelial cells, cardiomyocytes, monocytes, and macrophages. Crucially, ARA-290 does not activate the classical homodimeric EPOR responsible for erythropoiesis, thereby avoiding stimulation of red blood cell production. **Neuroprotective Signalling Cascades** Upon IRR activation, ARA-290 triggers multiple intracellular signalling pathways that promote cell survival and protect against damage: - JAK2/STAT5 pathway activation (cell survival signalling) - PI3K/Akt pathway engagement (anti-apoptotic effects) - NF-κB modulation (reduced inflammatory gene expression) - MAPK/ERK pathway involvement (cell proliferation and differentiation) **Anti-Inflammatory and Immunomodulatory Effects** ARA-290 modulates the innate immune response by shifting macrophage polarisation from the pro-inflammatory M1 phenotype toward the reparative M2 phenotype. This transition reduces production of inflammatory cytokines (TNF-α, IL-1β, IL-6) whilst increasing anti-inflammatory mediators (IL-10, TGF-β). The net effect is resolution of inflammation and promotion of tissue repair. **Small Fibre Nerve Protection and Regeneration** In clinical studies of sarcoidosis-related neuropathy, ARA-290 demonstrated the ability to significantly increase corneal small nerve fibre density (intraepidermal nerve fibre density did not change significantly in the same trial), alongside improved patient-reported neuropathic symptoms and 6-minute walk distance. This effect is proposed to be mediated through direct neuroprotective signalling in sensory neurons and Schwann cells, as well as indirect benefits from reduced neuroinflammation. **Metabolic Effects** Research has demonstrated that ARA-290 can improve metabolic parameters, potentially through effects on pancreatic beta cells and insulin sensitivity. IRR activation in metabolic tissues may contribute to improved glucose handling.

    Researched Benefits

    Based on preclinical and clinical research findings:

    • 1
      Increased corneal nerve fibre density in sarcoidosis patients with small fibre neuropathy in Phase II trials (intraepidermal nerve fibre density did not change significantly)
    • 2
      Reduction in neuropathic pain scores in clinical studies of sarcoidosis-related neuropathy
    • 3
      Anti-inflammatory effects through macrophage phenotype modulation without immunosuppression
    • 4
      Tissue-protective properties equivalent to EPO without haematopoietic stimulation or blood thickening
    • 5
      Potential cardioprotective effects observed in preclinical models of myocardial ischaemia
    • 6
      Improved metabolic parameters including glucose handling in research models
    • 7
      Neuroprotective effects in models of traumatic brain injury and stroke
    • 8
      Promotion of wound healing in diabetic ulcer models

    Claim vs Evidence

    How popular claims about ARA-290 stack up against the current research, graded using our public evidence grading methodology.

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Approved for neuropathy”ENoHighARA-290 is investigational with some encouraging Phase 2 data; not approved for any indication.

    Theoretical Dosing & Protocols

    ⚠️ Educational Only: The following information is derived from research literature and is not a prescription or recommendation. No standardised human dosing exists. Always consult a qualified healthcare professional.
    Theoretical Dosage2–4 mg per injection (based on clinical trial dosing, typically 2 mg in sarcoidosis studies)
    FrequencyDaily subcutaneous injection for 28 days (as per clinical trial protocols)
    Duration28 days in published clinical trials; optimal duration for various conditions not yet established
    NotesARA-290/cibinetide is an investigational compound that has been tested in controlled clinical trials. These protocols reflect trial designs and are not therapeutic recommendations. The peptide is not approved for any clinical use. Consult a qualified healthcare professional for guidance.

    Administration Routes

    Routes studied in research settings (educational only):

    • Subcutaneous injection (used in clinical trials)
    • Intravenous injection (used in some early-phase studies)
    Half-LifeStability
    Approximately 10–15 minutes (short plasma half-life, but biological effects persist for hours due to sustained intracellular signalling following receptor activation)Lyophilised powder stored at -20°C; reconstituted solution requires refrigeration at 2–8°C; relatively stable linear peptide structure

    Safety Profile & Known Risks

    Commonly Reported Side Effects

    • Injection site reactions (redness, mild discomfort)
    • Headache reported in some clinical trial participants
    • Mild gastrointestinal symptoms (nausea, abdominal discomfort)
    • Fatigue (uncommon but reported)

    Rare Risks & Concerns

    • Unknown long-term effects as clinical trial durations have been relatively short
    • Theoretical risk of immune modulation affecting responses to infection
    • Potential interactions with other immunomodulatory therapies not fully characterised
    • Allergic or hypersensitivity reactions (theoretical risk with any peptide)

    Contraindications

    • Known hypersensitivity to ARA-290 or any component of the formulation
    • Pregnancy and breastfeeding (insufficient safety data)
    • Active systemic infections (theoretical concern due to immune modulation)
    • Children and adolescents (no paediatric safety data established)
    • Concurrent use of erythropoiesis-stimulating agents (potential receptor interactions)

    UK & EU Regulatory Context

    🇬🇧 United Kingdom

    Investigational compound. Not licensed by the MHRA for any therapeutic indication.

    🇪🇺 European Union

    Not authorised by the EMA. Has received orphan medicinal product designation for sarcoidosis in the EU.

    ARA-290 (cibinetide) has been evaluated in multiple clinical trials and received orphan drug designation for sarcoidosis. Despite promising Phase II results, it has not yet achieved regulatory approval from any major authority. It is not available as a research chemical in the same manner as many research peptides — access has been primarily through clinical trial participation.

    Clinical Studies Summary

    A Randomised Double-Blind Placebo-Controlled Trial of ARA 290 in Sarcoidosis Patients with Small Fibre Neuropathy

    Phase II trial in 38 sarcoidosis patients with small nerve fibre loss: 28 days of ARA-290 (2 mg daily SC) significantly increased corneal nerve fibre density compared with placebo. Intraepidermal nerve fibre density (IENFD) at the thigh and distal leg did not change significantly in either group. ARA-290 significantly improved patient-reported neuropathic symptoms and increased 6-minute walk distance, and was well tolerated with no serious adverse events.

    Mol Med. 2013View on PubMed

    Managing fatigue in sarcoidosis - A systematic review of the evidence.

    Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended.

    Chron Respir Dis. 2017View on PubMed

    ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.

    In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was associated with a significant increase in corneal small nerve fibre density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. Intraepidermal nerve fibre density did not change significantly.

    Mol Med. 2013View on PubMed

    Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study.

    No change was observed in the IDS. ARA 290 appears to be safe in patients with sarcoidosis and can reduce neuropathic symptoms.

    Mol Med. 2012View on PubMed

    ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.

    Mean corneal nerve fiber density (CNFD) was reduced significantly compared with normal controls and subjects with a mean CNFD >1 standard deviation from normal showed a significant increase in CNFD compared with no change in the placebo group. These observations suggest that ARA 290 may benefit both metabolic control and neuropathy in subjects with type 2 diabetes and deserves continued clinical evaluation.

    Mol Med. 2015View on PubMed

    Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin.

    Despite a short plasma half-life (~2min), pHBSP activates a molecular switch that triggers sustained biological effects that have been observed in a number of experimental animal models of disease and in clinical trials. This review summarizes pharmacokinetic and pharmacodynamic data and discusses the molecular mechanisms underlying the long-lasting effects of this short-lived peptide.

    Pharmacol Ther. 2015View on PubMed

    Registered Trials & Regulatory Status

    Registered trials
    4
    Currently recruiting
    0
    Furthest phase
    Phase 2
    Approved product
    No

    1 of 2 completed trials have never posted results. Unreported trials are not neutral: results that go unpublished are more often negative ones.

    The Use of ARA290 for the Treatment of Diabetic Macular Oedema

    PHASE2

    Status: Terminated · 9 participants · Belfast Health and Social Care Trust

    Conditions: Diabetic Macular Oedema

    No results postedNCT06626971

    Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis

    PHASE2

    Status: Completed · 64 participants · Araim Pharmaceuticals, Inc.

    Conditions: Neuropathy of Sarcoidosis

    Results postedNCT02039687

    ARA290 in T2D (Effects of ARA 290, an Erythropoietin Analogue) in Prediabetes and Type 2 Diabetes)

    PHASE2

    Status: Unknown · 24 participants · Claes-Göran Östenson

    Conditions: Diabetes Type 2, Impaired Glucose Tolerance, Impaired Fasting Glucose

    No results postedNCT01933529

    Cognitive and Neural Effects of ARA290

    PHASE1/PHASE2

    Status: Completed · 36 participants · Leiden University Medical Center

    Conditions: Depression

    No results postedNCT02070783

    Adverse event reports (FDA FAERS)

    Not applicable: no licensed product contains this peptide, so it is not reported through FAERS. This is an absence of surveillance, not evidence of safety.

    Source: ClinicalTrials.gov and openFDA. Updated automatically.

    Looking for ARA-290?

    Source research-grade ARA-290 from a trusted UK supplier — third-party tested with certificate of analysis.

    View at Supplier

    Frequently Asked Questions

    Questions to ask a qualified clinician about ARA-290

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Are there UK trials of ARA-290 for my situation?
    • What licensed neuropathy treatments should I consider?

    UK regulatory & safety context

    Research peptides and UK law

    UK legal reference

    Unlicensed peptide risks

    Safety Centre guide

    Related Research Guides

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