At a Glance
| Feature | Detail |
|---|---|
| Name / structure | ARA-290, cibinetide; 11-amino-acid peptide (pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser) modelled on helix B of erythropoietin |
| Origin | Araim Pharmaceuticals (New York) with Leiden University Medical Center |
| Mechanism | Agonist of the innate repair receptor (EPO receptor plus beta common receptor, CD131): anti-inflammatory and tissue-protective, designed to spare red-cell production |
| Used for | Small fiber neuropathy (sarcoidosis, type 2 diabetes); off-label community use for neuropathic pain of other causes |
| Route | Subcutaneous (one trial used IV) |
| Typical dose range | Trials: 4 mg SC daily for 28 days (range 1–8 mg); practice protocols copy this |
| Evidence level | Emerging: small randomised trials (n = 22 to 64, 28 days each) with a consistent direction and objective surrogate endpoints; no phase 3 |
| Regulatory status | Not approved. FDA orphan designations (2011, neuropathic pain in sarcoidosis; 2016, sarcoidosis); EU orphan designation 2013; WADA 2026: prohibited (S0 and the S2.1.5 class) |
ARA-290 is one of the more serious molecules in the grey-market peptide catalogue. It came out of an academic-industry programme, was tested in randomised, placebo-controlled trials, and its effects were measured with an objective tool (corneal confocal microscopy) as well as questionnaires. The trials were also small and short, and the company behind them has gone quiet since around 2020.
The honest verdict: a mechanistically clever peptide with an early, consistent signal in small fiber neuropathy, and no confirmatory trial. People with burning feet who have been told nothing more can be done understandably find it. What they find is a 28-day protocol copied from phase 2.
How it works
Erythropoietin has two jobs. At high concentrations it binds the classic EPO receptor on bone-marrow precursors and drives red-cell production. At sites of injury, a different receptor assembles: the EPO receptor paired with the beta common receptor (CD131), called the innate repair receptor. Activating it dampens inflammation, protects cells from apoptosis and supports repair.
Attempts to use EPO itself for nerve or heart protection ran into its side effects: more red cells, thicker blood, clots. ARA-290 is a short peptide that reproduces the surface of EPO’s helix B, the part that engages the innate repair receptor, and leaves out the part that drives erythropoiesis. In rats with nerve injury it reduced allodynia for weeks and suppressed spinal microglial activation [6], which fits the idea that it acts on the neuroinflammation that keeps neuropathic pain going.
What the evidence shows
Human trials
| Study | Population | Design | n | Dose | Main finding |
|---|---|---|---|---|---|
| Heij 2012 [1] | Sarcoidosis with small fiber neuropathy symptoms | Randomised, double-blind, placebo-controlled pilot | 22 | 2 mg IV 3×/week for 4 weeks | Small fiber neuropathy screening score improved (−11.5 vs −2.9); SF-36 pain and physical functioning improved; pain and fatigue scores improved equally in both groups; no safety concerns |
| Dahan 2013 [2] | Sarcoidosis with documented small nerve fibre loss | Randomised, blinded, placebo-controlled | Small phase 2 | Daily SC for 28 days | Neuropathic symptoms improved; corneal nerve fibre density increased; 6-minute walk distance improved |
| Brines 2015 [3] | Type 2 diabetes with painful neuropathy | Randomised, placebo-controlled phase 2 | Small phase 2 | 4 mg SC daily for 28 days, followed to day 56 | Better HbA1c and lipids; PainDetect scores improved; corneal fibre density rose in those with the lowest baseline values; no safety issues |
| Culver 2017 [4] | Sarcoidosis with small fibre loss and neuropathic pain | Randomised, placebo-controlled phase 2b | 64 | 1, 4 or 8 mg SC daily for 28 days | Corneal nerve fibre area increased significantly only at 4 mg (placebo-corrected +697 µm²); regenerating skin fibres increased at 4 mg; pain improved in all groups including placebo |
| Lois 2020 [5] | Diabetic macular edema | Open-label phase 2 | 9 | 4 mg SC daily for 12 weeks | No improvement in vision or retinal thickness; safe; no anti-drug antibodies |
Read together, the direction is consistent across the three neuropathy trials, and the corneal nerve fibre data are objective. The caveats are just as consistent. Each trial lasted 28 days. The largest had 64 patients split across four arms. Pain improved in placebo groups too, which is typical of neuropathic pain trials, and the dose-response in the phase 2b was not linear (4 mg beat 8 mg). The developer sponsored the trials and co-authored the papers. The one clearly negative trial was in the eye.
How the nerve measurements work
Small fiber neuropathy affects the thinnest sensory and autonomic fibres, which standard nerve conduction tests miss. Two tools carry the ARA-290 data. Corneal confocal microscopy photographs the nerve plexus in the cornea, the most densely innervated tissue in the body, in a few minutes and without a needle; a 2022 meta-analysis of 38 studies with about 4,000 participants found that it reliably detects small fibre loss in diabetic neuropathy, including in early stages [10]. Skin biopsy counts intraepidermal nerve fibres and, with the GAP-43 stain used in the phase 2b trial, regenerating fibres [4].
That matters for how to read the trials. Questionnaires about burning and tingling respond strongly to placebo; the corneal and skin measures do not. The fact that corneal fibre area and regenerating skin fibres moved at 4 mg, and that these changes correlated with each other and with walking distance [4], is the most interesting signal in the programme. It is still a 28-day surrogate change, and nobody has shown that it predicts lasting relief.
What is not known
Whether the effect lasts beyond a month, whether repeated cycles help, whether it works in idiopathic, chemotherapy-induced or post-viral small fiber neuropathy, and what happens with long-term use. The Leiden group laid out the case for a larger trial in 2014 [7]. That trial has not been published.
Dosing
For informational purposes only — this summarises doses used in research and practice; it is not a prescription or individual medical advice.
| Goal | Dose | Route | Frequency / timing | Cycle length | Basis |
|---|---|---|---|---|---|
| Small fiber neuropathy (sarcoidosis) | 2 mg | IV | 3× weekly | 4 weeks | Trial [1] |
| Small fiber neuropathy (sarcoidosis, type 2 diabetes) | 4 mg | SC | Once daily | 28 days | Trial [3][4] |
| Dose range tested | 1, 4 or 8 mg | SC | Once daily | 28 days | Trial [4] (4 mg most effective) |
| Neuropathic pain, any cause (community standard) | 4 mg (some use 1–4 mg) | SC | Once daily | 28 days, then 28 days off, repeated if helpful | Practice protocol (peptidedosingprotocols.com, Jay Campbell, r/smallfiberneuropathy) |
| Intermittent variant | 2 mg, may rise to 4 mg | SC | 2–3× weekly (e.g. Mon/Wed/Fri) | Reassess at 4–6 weeks | Practice protocol (compounding pharmacy explainer, Path to Peptides) |
| Titration | 0.5 → 1 → 2 → 3 → 4 mg daily | SC | Step up every few days | Then a 28-day course | Anecdotal (r/PeptideForum) |
Community stacks combine ARA-290 with other “nerve” agents, which makes any effect impossible to attribute. If you want to know whether it does anything for you, one agent at a time and a symptom diary before, during and after the course is the minimum.
For injection technique, see the peptide injection guide.
What people report: what works and what doesn’t
Reported to work
- Less burning, numbness and tingling, and better temperature sensation, often noticed in weeks 1 to 3 of a 4 mg daily course (r/neuropathy, r/smallfiberneuropathy).
- Long COVID users describe partial calming of nerve pain over repeated 28-day rounds (r/covidlonghaulers).
Mixed or unclear
- Relief is often partial (one experienced user estimates about a quarter), fades after stopping, and some describe tolerance that prompts breaks between cycles (r/smallfiberneuropathy).
- Cost is the main reason people stop or ration it.
Reported not to work, or disappointing
- No relief after 14 days, 6 weeks, 8 weeks or a full course (r/smallfiberneuropathy, r/PeptideForum).
- A recurring theme is a temporary flare: new shooting or jolting pain and muscle twitching, which users tend to read as nerve regeneration. That interpretation is unproven.
What a proper trial would need to show: a sustained reduction in pain and an increase in nerve fibre density beyond 3 months, in a phase 3 population large enough to separate the effect from the strong placebo response seen in neuropathic pain.
Safety and side effects
In the published trials (28-day courses, plus one 12-week eye study), no safety signal emerged and the eye study found no anti-drug antibodies [1–5]. Because the peptide was engineered not to stimulate red-cell production, the polycythaemia and clotting risks of EPO are not expected, but nobody has followed users for years.
Unknowns worth naming: long-term use, use in people with active cancer, pregnancy, and interactions with the immunosuppressants used in sarcoidosis. Grey-market supply adds the usual problems: wrong content, impurities, endotoxin and non-sterile vials.
Before anyone reaches for an experimental peptide, the neuropathy itself deserves a proper work-up, because treatable causes are common and some are serious:
- Blood tests: fasting glucose and HbA1c (or a glucose tolerance test, since impaired glucose tolerance alone can cause small fibre neuropathy), vitamin B12, thyroid function, kidney and liver function, and protein electrophoresis with immunofixation.
- Depending on the picture: autoimmune screens (Sjögren’s, coeliac disease), sarcoidosis work-up, HIV and hepatitis C, alcohol and medication history (including chemotherapy and some antibiotics), and genetic testing in familial cases.
- Confirmation of the diagnosis itself with skin biopsy or corneal confocal microscopy where available.
Treating the cause (tight glucose control, B12 replacement, immunotherapy in immune-mediated forms) changes outcomes; ARA-290 has not been shown to.
Legal and regulatory status
- United States. Not approved. FDA granted orphan drug designation for the treatment of neuropathic pain in patients with sarcoidosis on 13 September 2011 [9], and a further designation for sarcoidosis in 2016. It is not on the 503A bulks list, so it has no legitimate compounding route.
- EU and Germany. EU orphan designation EU/3/13/1191 for sarcoidosis (2013); no marketing authorisation. Supply for human use outside a trial is supply of an unauthorised medicine.
- Development. ClinicalTrials.gov lists completed phase 2 trials and none active. The developer’s last public news dates from 2020.
- Sport. Prohibited at all times. As a non-approved substance it falls under WADA S0, and as an innate repair receptor agonist it matches S2.1.5 of the 2026 Prohibited List [8].
How it fits
ARA-290 belongs to a different category from the healing peptides most people know. BPC-157 and TB-500 are marketed for tendon and tissue repair with very little human trial data. ARA-290 has fewer users but more and better human data, for a narrower question: small fibre nerve damage. For peripheral neuropathy, other options covered on this site include photobiomodulation and benfotiamine. None of them, ARA-290 included, replaces finding and treating the cause.
Related Articles
- Photobiomodulation for Peripheral Neuropathy
- Benfotiamine for Peripheral Neuropathy
- Peptides for Autoimmune Disease
- Peptide Injection Guide
- Peptides and WADA Anti-Doping Rules
Frequently asked questions
What is ARA-290 used for?
ARA-290 (cibinetide) was developed for small fiber neuropathy, especially in sarcoidosis, and was also tested in type 2 diabetes with painful neuropathy and in diabetic macular edema. Outside trials, people use it for neuropathic pain from many causes, including long COVID, without trial evidence for those uses.
What dose of ARA-290 was used in trials?
Trials used 2 mg intravenously three times a week for 4 weeks, or 1, 4 or 8 mg subcutaneously once daily for 28 days. The 4 mg daily dose showed the clearest effect on nerve fibre measures in the largest trial.
Does ARA-290 raise hemoglobin like EPO?
It was designed to activate the tissue-protective receptor without driving red blood cell production, and the published trials reported no safety concerns. Long-term data are missing.
Is ARA-290 FDA approved?
No. It has US orphan drug designations for neuropathic pain in sarcoidosis and for sarcoidosis, and an EU orphan designation for sarcoidosis. A designation is not an approval, and no phase 3 trial has been completed.
Is ARA-290 banned in sport?
Yes. It is not approved anywhere, so WADA's S0 class applies, and as an innate repair receptor agonist it also matches the S2.1.5 category of the 2026 Prohibited List. It is prohibited at all times.
References
- 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. PMID: 23168581. https://pubmed.ncbi.nlm.nih.gov/23168581/
- Dahan A, Dunne A, Swartjes M, et al. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med. 2013. PMID: 24136731. https://pubmed.ncbi.nlm.nih.gov/24136731/
- 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. PMID: 25387363. https://pubmed.ncbi.nlm.nih.gov/25387363/
- 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. PMID: 28475703. https://pubmed.ncbi.nlm.nih.gov/28475703/
- Lois N, Gardner E, McFarland M, et al. A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema. J Clin Med. 2020. PMID: 32674280. https://pubmed.ncbi.nlm.nih.gov/32674280/
- Swartjes M, van Velzen M, Niesters M, et al. 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. PMID: 24529189. https://pubmed.ncbi.nlm.nih.gov/24529189/
- van Velzen M, Heij L, Niesters M, et al. ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig Drugs. 2014. PMID: 24555851. https://pubmed.ncbi.nlm.nih.gov/24555851/
- World Anti-Doping Agency. The 2026 Prohibited List (S0; S2.1.5 innate repair receptor agonists), as published in Tractatenblad 2026, 25. https://zoek.officielebekendmakingen.nl/trb-2026-25.html
- U.S. Food and Drug Administration. Orphan Drug Designations and Approvals: L-pyr-L-glu-L-gln-L-leu-L-glu-L-arg-L-ala-L-leu-L-asn-L-ser-L-ser, treatment of neuropathic pain in patients with sarcoidosis (designated 13 September 2011). https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=349111
- Gad H, Petropoulos IN, Khan A, et al. Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta-analysis. J Diabetes Investig. 2022. PMID: 34351711. https://pubmed.ncbi.nlm.nih.gov/34351711/
Disclaimer: This article is for information and education only and is not a prescription or individual medical advice. ARA-290 is not an approved medicine.
