ARA-290

Cibinetide, ARA 290, pHBSP (pyroglutamate helix B surface peptide), helix B surface peptide

Recovery, repair & tissue

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Synthetic 11-amino-acid peptide modelled on one surface of the erythropoietin (EPO) molecule
Mechanism: Activates the "innate repair receptor" (a pairing of the EPO receptor with the β-common receptor CD131) that is switched on in injured tissue, producing EPO's tissue-protective effects without stimulating red blood cell production
Routes studied: Subcutaneous (human trials); intravenous and intraperitoneal (animal)
Dose range reported: Human trials: 2 mg and 4 mg subcutaneous once daily for 28 days (sarcoidosis neuropathy, type 2 diabetes neuropathy); single doses up to higher levels in Phase 1. Community reports mirror the 4 mg/day trial dose, sometimes shorter courses. Not approved; no label dose
Half-life: Very short in plasma — about 2 minutes — yet effects in trials persisted for weeks, consistent with a receptor that is only present on stressed cells
Storage: Lyophilised: refrigerate. Reconstituted: refrigerate; community practice is use within ~4 weeks
Regulatory status: Investigational. Orphan designation in the US for sarcoidosis-associated neuropathy; not approved anywhere. See region table

Doses are as reported in studies or by the community — never recommendations.

1What it is

Erythropoietin (EPO) is the hormone that drives red blood cell production, but it also protects tissue from injury — in the brain, heart, kidney and nerves. Using EPO for protection is impractical because it also raises haemoglobin and clotting risk. In the 2000s a team led by Michael Brines and Anthony Cerami worked out that the two actions used different receptors, and designed a short peptide copying the part of EPO (helix B) that faces the tissue-protective receptor but not the classical EPO receptor. That peptide is ARA-290, later given the generic name cibinetide.

It has been through Phase 1 and several Phase 2 trials, mostly in small-fibre neuropathy — damage to the thin nerve fibres that carry pain and temperature and regulate sweating and blood flow. It is unusual on this site in having placebo-controlled human data, though the trials are small and the drug has not been approved.

2How it's thought to work

Innate repair receptor. ARA-290 binds a heterodimer of the EPO receptor and CD131 (the β-common receptor). This complex is barely present on healthy cells and appears on cells under stress — injury, hypoxia, inflammation — so the peptide acts mostly where damage is (Brines 2008).

No erythropoiesis. it does not activate the classical EPO receptor homodimer, so it does not raise haemoglobin or haematocrit. Confirmed in human trials.

Downstream effects. reduced apoptosis, reduced pro-inflammatory cytokine release, and in nerve studies, regrowth of small fibres measured in the cornea and skin.

Metabolic effects. in diabetic patients it improved HbA1c and cholesterol modestly; the mechanism is proposed to involve reduced inflammation in pancreatic islets and adipose tissue.

An eleven-amino-acid peptide copying the part of erythropoietin that binds the innate repair receptor, a different receptor from the one that makes red cells. It reaches the tissue-protective effects of EPO without raising haematocrit.Schematic — not to scale

3What the research shows

Graded A (small)

Sarcoidosis-associated small-fibre neuropathy

A pilot randomised, double-blind, placebo-controlled study (n=22) reported improved neuropathic symptoms and quality of life after 4 weeks of 2 mg daily ARA-290 (Heij 2012, Mol Med). A follow-up Phase 2 trial (n≈40) reported improved symptoms and increased corneal nerve fibre density (Dahan 2013, Mol Med). A larger Phase 2b trial (n=64) with 1, 4 and 10 mg daily for 28 days found the 4 mg dose increased corneal nerve fibre area and improved some functional measures; patient-reported pain endpoints were less consistent (Culver 2017, Front Neurol). [2][3][5]

Graded A (small)

Type 2 diabetes with neuropathy

Randomised, placebo-controlled, 28-day trial of 4 mg daily (n=48): improved neuropathic symptoms, lower HbA1c and improved lipid profile relative to placebo; no change in haemoglobin (Brines 2015, Mol Med). [4]

Tissue protection in organ injury

Rodent models of stroke, myocardial infarction, kidney ischaemia-reperfusion and wound healing report reduced damage (Brines 2008, PNAS; multiple subsequent rodent papers). A clinical trial in kidney transplantation has been conducted; results should be checked before citing †. [1]

Pharmacokinetics and safety in healthy volunteers

Phase 1 single- and multiple-dose studies in healthy adults established the very short plasma , linear kinetics and absence of haematological effects at doses above those later used in Phase 2. Published mainly as summaries within the later trial papers and company disclosures †.

Long-term outcomes, larger populations

No Phase 3 trial has been completed. The largest controlled exposure is a few dozen patients for 28 days. Development has moved between sponsors (Araim Pharmaceuticals and partners) and the current status of any late-phase programme should be checked before publishing †.

Other proposed uses

Community discussion extends ARA-290 to tendon healing, "mitochondrial support" and general recovery. None of these has been studied in humans; the rodent organ-injury models are the only basis.

4Reported side effects and interactions

Literature-reported

In Phase 1 and 2 trials ARA-290 was well tolerated; adverse events were similar to placebo. No effect on haemoglobin, haematocrit, platelets or blood pressure was observed — the key safety distinction from EPO. Injection-site reactions were mild.

Community-reported

generally few; some report transient fatigue or headache, injection-site redness. Several members report subjective improvement in neuropathic pain or temperature sensation; others report nothing.

Theoretical. anything that protects stressed cells from dying could, in principle, protect tumour cells; this has not been observed but has not been studied over the long term. Immunogenicity to a synthetic EPO-derived peptide has not been reported.

Interactions. none established. It does not add to the erythropoietic effect of EPO analogues.

Markers researchers commonly monitor

Marker	Why it's watched
Haemoglobin / haematocrit	to confirm the absence of an erythropoietic effect, which is the defining safety property of this peptide versus EPO.
HbA1c and fasting glucose	the diabetes trial showed modest improvement; also relevant to anyone with metabolic disease.
Lipid panel	improved total and LDL cholesterol in the diabetes trial.
Small-fibre neuropathy measures (corneal confocal microscopy, skin biopsy nerve fibre density, quantitative sensory testing)	the trial endpoints; not routinely available but the only objective readout of the main effect.
Blood pressure	unchanged in trials; a useful contrast with EPO.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Typically supplied in 10 mg or 16 mg vials because trial doses are in milligrams, not micrograms — a 4 mg dose uses a large share of a vial, so concentration maths matters. with , swirl gently.

Open in calculator, pre-loaded →

6Commonly studied alongside

Not typically combined in the literature. Community discussion pairs it with BPC-157 or alpha-lipoic acid in neuropathy contexts; no combined study.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Investigational; orphan drug designation for sarcoidosis-associated small-fibre neuropathy †
European Union	Not authorised; orphan designation history †
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Prohibited by WADA under S2 — the list names innate repair receptor agonists derived from EPO (e.g. asialo-EPO, carbamylated EPO) and ARA-290 is treated as one of these †

8Open questions

Will a Phase 3 trial confirm the symptomatic benefit, and in which patient group?
How can a 2-minute plasma produce effects lasting weeks — is the receptor model fully correct?
Long-term safety beyond 28 days: no data.

9References

1Brines M et al. (2008). Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci USA. PubMed · DOI
2Heij L et al. (2012). Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med. PubMed · DOI
3Dahan A et al. (2013). ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med. PubMed · DOI
4Brines M et al. (2015). ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med. PubMed · DOI
5Culver DA et al. (2017). Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain. Front Neurol. PubMed · DOI
6Brines M, Cerami A (2012). The receptor that tames the innate immune response. Mol Med. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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community protocols include this →

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

25 Oct 2026Profile published — awaiting medical review

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