Erythropoietin (EPO) is famous for one job: telling the body to make red blood cells. But EPO also protects tissues from injury through a separate receptor, and that second job is the one ARA-290 was built to keep. It is an 11-amino-acid fragment of EPO designed to switch on tissue repair without raising red cell production.
This guide explains how ARA-290 (cibinetide) works, what its phase 2 trials in nerve damage found, where development stands, and what to check before ordering it in Canada.
The short answer
- ARA-290, also called cibinetide, is an 11-amino-acid peptide engineered from the helix-B surface of erythropoietin by Michael Brines and Anthony Cerami.
- It activates the innate repair receptor, a pairing of the EPO receptor with the beta-common receptor (CD131), without binding the classic EPO receptor that drives red blood cell production.
- In mice with nerve injury it relieved pain-like hypersensitivity, but not in mice lacking the beta-common receptor.
- Phase 2 trials at Leiden University Medical Center in sarcoidosis-associated small-fibre neuropathy reported improved symptoms and regrowth of corneal nerve fibres.
- It is not an approved medicine. Research-grade ARA-290 is a laboratory reagent.
ARA-290 (cibinetide)
Also called pHBSP, pyroglutamate helix B surface peptide.
- Length
- 11 amino acids
- Origin
- The helix-B surface of erythropoietin
- Receptor
- Innate repair receptor: EPO receptor plus CD131
- Developed by
- Michael Brines and Anthony Cerami; first described in 2008
- Clinical research
- Phase 2 trials in small-fibre neuropathy (sarcoidosis, type 2 diabetes)
Where the evidence stands
- Cell studies
- Animal studies
- Human studies
- Controlled clinical trials
Phase 2 only, with trials generally under 100 patients. Not an approved medicine.
EPO’s double life
Classic EPO signalling runs through a receptor made of two EPO receptor units, found on red blood cell precursors in the bone marrow. That is the pathway behind EPO’s medical use in anaemia, and behind its abuse in endurance sport. Brines and Cerami showed that EPO also protects injured tissues through a different receptor: an EPO receptor unit paired with the beta-common receptor, CD131. They named it the innate repair receptor because it switches on anti-inflammatory and tissue-repair pathways at once.
Designing ARA-290
In a 2008 paper in the Proceedings of the National Academy of Sciences, Brines and colleagues described engineering short peptides from the three-dimensional surface of EPO that faces the innate repair receptor, part of the molecule’s helix B. ARA-290 is the 11-residue result. It selectively activates the repair receptor without binding the classic EPO receptor, so it is designed not to stimulate red blood cell production.
In mouse studies of sciatic nerve injury, ARA-290 produced rapid and lasting relief of mechanical and cold hypersensitivity in normal mice, but not in mice lacking the beta-common receptor. That knockout result is strong evidence that CD131 is required for its effect.
Research-grade ARA-290 with a batch-matched COA.
View ARA-290What the trials found
Most of the human evidence comes from a program led by Albert Dahan’s group at Leiden University Medical Center in the Netherlands, in patients with small-fibre neuropathy, damage to the smallest sensory and autonomic nerves that causes pain and other symptoms.
- 2012A pilot trial in sarcoidosis patients with small-fibre neuropathy reports improved symptoms.
- 2013A blinded, placebo-controlled trial published in Molecular Medicine reports that 28 days of ARA-290 improved neuropathic symptoms, increased the density of small nerve fibres in the cornea and improved six-minute walking distance.
- 2015A trial in people with type 2 diabetes and neuropathy reports improved neuropathic symptoms and metabolic measures.
- 2017A larger phase 2b study in sarcoidosis, published in Investigative Ophthalmology & Visual Science, reports increased corneal nerve fibre abundance.
Nerve fibres regrew in the cornea, measured with a microscope that images the eye, but not in skin biopsies. The trials were small, generally under 100 patients, and the compound has not progressed to approval.
What is established and what is open
Reasonably well established
- ARA-290 targets the innate repair receptor, not the classic EPO receptor.
- Its effect in nerve-injury mice requires the beta-common receptor.
- Small phase 2 trials reported symptom improvement and corneal nerve regrowth.
Open questions
- Whether the phase 2 results would hold in larger, longer trials.
- Why nerve regrowth appeared in the cornea but not the skin.
- How the innate repair receptor behaves across other tissues.
Related repair and immune research peptides
ARA-290Innate repair receptor agonistView product and COA
Thymosin alpha-1Thymic immune peptideView product and COA
LL-37The human cathelicidinView product and COA
BPC-157Repair-research pentadecapeptideView product and COA
Sourcing ARA-290 in Canada
Before ordering ARA-290 from any supplier, check that:
- Identity is confirmed by mass spectrometry. ARA-290 begins with a pyroglutamate, a cyclized residue that changes the expected mass, so the COA should match the pyroglutamate form. See HPLC vs mass spectrometry.
- Purity is reported by HPLC and the COA matches your lot. How to read a certificate of analysis walks through it.
- Storage is cold, dry and dark. See our peptide storage guide.
Research use only. ARA-290 from Pure Peptides Canada is a laboratory reagent. It is not an approved drug, it is not for human or veterinary use, and nothing in this article is dosing or medical guidance.
Frequently asked questions
What is ARA-290?
ARA-290 is an 11-amino-acid peptide engineered from the helix-B surface of erythropoietin. It activates the innate repair receptor, which drives tissue protection and anti-inflammatory signalling, without activating the classic EPO receptor.
Is ARA-290 the same as cibinetide?
Yes. Cibinetide is the international nonproprietary name for ARA-290. It is also called pHBSP, short for pyroglutamate helix B surface peptide.
Does ARA-290 raise red blood cell production?
It was designed not to. ARA-290 binds the innate repair receptor (EPO receptor plus CD131) rather than the classic EPO receptor that drives red blood cell production.
What clinical trials has ARA-290 been in?
Phase 2 trials, mostly at Leiden University Medical Center, in small-fibre neuropathy associated with sarcoidosis or type 2 diabetes. They reported improved symptoms and corneal nerve fibre regrowth, but were small, and the compound has not been approved.
Is ARA-290 approved in Canada?
No. ARA-290 is not an authorized drug in Canada or elsewhere. Pure Peptides Canada sells it strictly as a laboratory research reagent that is not for human or veterinary use.
Does Pure Peptides Canada ship ARA-290 across Canada?
Yes. Orders ship tracked and discreetly across Canada, usually arriving by Xpresspost in 3–7 days, or free in 4–12 days on orders over $299, with free shipping on orders over $299.
ARA-290, tested batch by batch
Lyophilized ARA-290 with an independent COA for every batch, tracked delivery across Canada and pricing in Canadian dollars.
References
- Brines M, et al. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci USA. 2008.
- 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. DOI
- 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.
- 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.
- Dahan A, Brines M, Niesters M, Cerami A, van Velzen M. Targeting the innate repair receptor to treat neuropathy. Pain Rep. 2016. PubMed Central
For laboratory research use only. Not for human or veterinary use. This article summarizes published research for educational purposes and is not medical advice. Nothing here is intended to diagnose, treat, cure or prevent any disease.