ARA-290
An 11-amino-acid peptide modelled on erythropoietin's helix B: tissue protection in animals without red-cell stimulation, and small phase 2 trials in sarcoidosis neuropathy
ARA 290, also called cibinetide, is an 11-amino-acid peptide modelled on one face of erythropoietin (EPO). It is designed to activate the tissue-protective receptor complex that EPO forms with the β-common receptor, not the receptor that drives red-cell production. In animals it reduced inflammation, pain behaviour and injury to kidney, brain and gut. In people it has been tested only in small phase 2 trials, mainly in sarcoidosis with small-fibre nerve loss, where four weeks of treatment improved symptoms and corneal nerve measures. It is not approved anywhere.
What is it?
Erythropoietin does two jobs through two different receptors. Through a pair of EPO-receptor chains it tells the bone marrow to make red blood cells; through a complex of the EPO receptor and the β-common receptor (CD131) it protects tissues from injury. High doses of EPO bring the first effect along with the second: after kidney transplantation, high-dose EPO did not improve short-term outcomes and increased the risk of thrombotic events. In 2008 scientists at Warren Pharmaceuticals showed that an 11-amino-acid peptide reproducing the aqueous face of EPO's helix B protected tissue in animal models without stimulating red-cell production. ARA 290 is that peptide.
In animals the idea largely held. After stroke in mice, ARA 290 reduced neuronal death and inflammatory cytokines, and knocking down the β-common receptor removed the protection. It improved kidney function and reduced fibrosis after renal ischaemia in pigs, lowered disease activity and deaths in experimental colitis by damping macrophage inflammation, improved wound healing in diabetic mice, and blocked the capsaicin receptor TRPV1 in pain experiments.
The human trials are small and short. In sarcoidosis with painful small-fibre neuropathy, 22 patients given 2 mg intravenously three times a week for four weeks improved on a neuropathy symptom screening list against placebo, and a trial of daily injections under the skin reported better symptoms, more corneal nerve fibres and a longer six-minute walk. The largest trial, a 64-patient phase 2b, met its primary endpoint only at the middle dose: corneal nerve fibre area rose by 697 µm² against placebo at 4 mg a day, with no significant change at 1 or 8 mg. A 28-day trial in type 2 diabetes with painful neuropathy reported better HbA1c, lipids and neuropathy scores.
Elsewhere it did less. In nine patients with diabetic macular oedema, 12 weeks of treatment did not improve vision or retinal thickness, and in 36 healthy volunteers a single dose did not produce an antidepressant-like profile. No safety concern was reported in these trials, but each was small and lasted weeks, not years. ARA 290 is not approved anywhere: FDA's Drugs@FDA database holds no application for cibinetide, and EMA's register of centrally authorised medicines has no entry.
Mechanism of Action
ARA 290 is built to use one of erythropoietin's two receptor systems and not the other.
The innate repair receptor
Outside the bone marrow, the EPO receptor pairs with the β-common receptor (CD131). In mouse macrophages ARA 290's anti-inflammatory effects depended on CD131 and JAK2 and worked by inhibiting the NF-κB subunit p65; in mice with stroke, silencing the β-common receptor abolished its protection.
No red-cell stimulation
Red-cell production runs through EPO-receptor homodimers. Neither helix B nor the 11-amino-acid peptide was erythropoietic in the 2008 experiments, and in the 2024 mouse stroke study ARA 290 protected brain tissue without causing erythropoiesis.
Damping inflammation
In experimental colitis it reduced the influx of myeloid cells and the production of cytokines, chemokines and nitric oxide synthase-2; after stroke it lowered inflammatory cytokines and neuronal apoptosis; after renal ischaemia in pigs it tended to reduce MCP-1 and IL-6.
Pain signalling
In cell and behavioural experiments it inhibited the capsaicin receptor TRPV1 directly and relieved capsaicin-induced mechanical hypersensitivity, a route to pain relief separate from its anti-inflammatory effects.
Published Research
These are the studies that describe ARA 290, read from their PubMed abstracts: the phase 2 trials in sarcoidosis neuropathy, type 2 diabetes and diabetic macular oedema, a volunteer study of emotional processing, and the animal work behind them. Every human trial was small and lasted weeks.
Phase 2b in sarcoidosis: 64 patients, three doses
Patients with sarcoidosis-associated small nerve fibre loss and neuropathic pain took 1, 4 or 8 mg a day or placebo for 28 days. The placebo-corrected gain in corneal nerve fibre area was 109 µm² (95% CI -429 to 647), 697 (159 to 1,236; P=0.012) and 431 (-130 to 992) by dose; regenerating skin fibres increased at 4 mg (P=0.035). Pain improved significantly in all groups, and changes in nerve fibre area correlated with the six-minute walk.
Pilot: intravenous dosing in 22 sarcoidosis patients
Patients with sarcoidosis and small-fibre neuropathy symptoms received 2 mg intravenously three times a week (12) or placebo (10) for four weeks. The small-fibre neuropathy screening score improved by 11.5 points against 2.9 on placebo (P<0.05), and SF-36 pain and physical functioning improved from baseline; pain inventory and fatigue scores improved equally in both groups. No safety concerns were raised.
Daily injections in sarcoidosis nerve fibre loss
In a blinded, placebo-controlled trial, 28 days of daily subcutaneous ARA 290 in patients with documented small nerve fibre loss significantly improved neuropathic symptoms and was associated with an increase in corneal small nerve fibre density, changes in skin temperature sensitivity and a longer six-minute walk. The abstract gives no patient numbers.
Type 2 diabetes with painful neuropathy
In a phase 2 trial, subjects self-injected 4 mg or placebo daily for 28 days and were followed for a further month. The ARA 290 group improved in HbA1c and lipid profiles across the 56 days and in neuropathic symptoms on the PainDetect questionnaire; corneal nerve fibre density rose in those whose baseline density was more than one standard deviation below normal. No potential safety issues were identified.
Diabetic macular oedema: nine patients, 12 weeks
Patients with diabetic macular oedema thicker than 400 µm self-injected 4 mg daily for 12 weeks in Belfast; eight of nine completed. Mean visual acuity (-2.9 letters), retinal thickness (+10 µm), retinal sensitivity and tear production did not improve, while a visual-function questionnaire score rose 2.7 points. There were no serious adverse events and no antibodies to cibinetide.
Emotional processing in 36 healthy volunteers
In a double-blind randomised study, a single 2 mg dose or placebo was followed a week later by brain imaging and emotion tests. ARA 290 lowered neural responses to happy faces, sped categorisation of positive words and increased attention to positive pictures, without changing mood; the authors concluded that the effects do not clearly support an antidepressant-like profile.
Two phase 2 trials in sarcoidosis, reviewed
Written by investigators from the trials, the review reports that ARA 290 was consistently associated with lower neuropathic pain scores in sarcoidosis patients, with increases in corneal nerve fibres and improved pain thresholds, quality of life and physical functioning, and calls for studies of whether it modifies the disease.
Stroke in mice, through the β-common receptor
After middle cerebral artery occlusion and reperfusion, ARA 290 was neuroprotective in a way qualitatively similar to EPO, reducing neuronal apoptosis and inflammatory cytokines in brain tissue. Silencing the β-common receptor with siRNA significantly suppressed the protection, and ARA 290 did not cause erythropoiesis.
Experimental colitis in mice
Cibinetide reduced myeloid-cell infiltration and pro-inflammatory cytokines, chemokines and nitric oxide synthase-2, lowering disease activity and mortality. In activated macrophages its anti-inflammatory effect required CD131 and JAK2 and ran through inhibition of the NF-κB subunit p65.
Kidney ischaemia in pigs
Eight pigs had one kidney made ischaemic for 45 minutes and received ARA 290 or saline intravenously at 0, 2, 4 and 6 hours after reperfusion. ARA 290 increased glomerular filtration over the following seven days, tended to lower MCP-1 and IL-6 at 15 minutes, and reduced interstitial fibrosis at day 7.
Impaired wound healing in diabetic mice
In diabetic mice, wounds treated with vehicle showed low VEGF, phosphorylated Akt and eNOS signalling, with poor re-epithelialisation, blood-vessel growth and wound strength. Cibinetide significantly improved these abnormalities, which the authors attribute to activation of the EPO receptor and β-common receptor complex.
Pain and the TRPV1 channel
Using calcium imaging, cell culture and behavioural tests, the authors found that ARA 290 specifically inhibited TRPV1 channel activity and relieved mechanical hypersensitivity induced by capsaicin, suggesting it could also act directly on pain-sensing neurons.
Dosing Data
ARA 290 is not approved, so the only doses are those its trials used, all for weeks rather than months.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
ARA 290 has no label. These cautions follow from how little has been tested; they are not instructions.
Legal Status
ARA 290 (cibinetide) is an investigational drug that no regulator has approved.
Frequently Asked Questions
?Is ARA 290 the same as EPO?
No. It is an 11-amino-acid peptide modelled on one face of EPO. It is designed to activate EPO's tissue-protective receptor complex, which includes the β-common receptor, without the receptor that drives red-cell production; in a mouse stroke study it protected the brain without causing erythropoiesis.
?Does ARA 290 help neuropathy?
In small four-week trials in sarcoidosis it improved neuropathy symptoms and increased corneal nerve fibres. Its largest trial, 64 patients, met its primary endpoint at 4 mg a day but not at 1 or 8 mg, and no larger or longer trial has been published.
?Is ARA 290 approved?
No. FDA's Drugs@FDA database has no application for cibinetide and EMA's register has no entry, as of September 30, 2026.
?What doses were used in trials?
2 mg into a vein three times a week in the first sarcoidosis trial, 1 to 8 mg under the skin daily for 28 days in later ones, and 4 mg daily for 12 weeks in the macular oedema trial. These are trial doses, not recommendations.
?Is it safe?
No safety concern was reported in its trials, but they were small and lasted 4 to 12 weeks, so uncommon or long-term effects are unknown.
?Why is it called cibinetide?
ARA 290 was its development code; later trial reports use the name cibinetide. The same molecule also appears as pHBSP, for pyroglutamate helix B surface peptide.
References
- [pubmed] Culver DA, 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. PMID: 28475703.
- [pubmed] Heij L, 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(1):1430-6. PMID: 23168581.
- [pubmed] Dahan A, et al. "ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density." Mol Med, 2013;19(1):334-45. PMID: 24136731.
- [pubmed] Brines 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(1):658-66. PMID: 25387363.
- [pubmed] Lois N, et al. "A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema." J Clin Med, 2020;9(7). PMID: 32674280.
- [pubmed] Cerit H, et al. "Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action." Eur Neuropsychopharmacol, 2015;25(12):2289-99. PMID: 26431906.
- [pubmed] van Velzen M, et al. "ARA 290 for treatment of small fiber neuropathy in sarcoidosis." Expert Opin Investig Drugs, 2014;23(4):541-50. PMID: 24555851.
- [pubmed] Wang RL, et al. "Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke." CNS Neurosci Ther, 2024;30(3):e14676. PMID: 38488446.
- [pubmed] Nairz M, et al. "Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis." Sci Rep, 2017;7(1):13012. PMID: 29026145.
- [pubmed] van Rijt WG, et al. "ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury." J Transl Med, 2013;11:9. PMID: 23302512.
- [pubmed] Bitto A, et al. "Activation of the EPOR-β common receptor complex by cibinetide ameliorates impaired wound healing in mice with genetic diabetes." Biochim Biophys Acta Mol Basis Dis, 2018;1864(2):632-639. PMID: 29223734.
- [pubmed] Zhang W, et al. "ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception." Peptides, 2016;76:73-9. PMID: 26774587.
- [pubmed] Brines M, et al. "Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin." Proc Natl Acad Sci U S A, 2008;105(31):10925-30. PMID: 18676614.
- [fda] FDA. Drugs@FDA (openFDA): no application for cibinetide (ARA 290). Read September 30, 2026.
- [other] European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for cibinetide. Read September 30, 2026.
Sources & Citations
Every study on this page was read from its PubMed record, including the 2008 paper that designed the peptide. Approval status comes from FDA's Drugs@FDA database and EMA's register, read September 30, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.