ARA-290 peptide (cibinetide): what the human trials actually found

ARA-290 is a short synthetic peptide built from part of the erythropoietin molecule. Erythropoietin, or EPO, is best known as the hormone that tells bone marrow to make red blood cells, and as a drug abused in endurance sport. But EPO also has a separate, local role: tissue made or exposed to EPO resists injury. The two jobs run through different receptors. Red cell production works through a pair of EPO receptors joined together, while tissue protection works through a mixed receptor made of the EPO receptor plus CD131, the beta common receptor, a complex its developers named the innate repair receptor ^[1].

In 2008 a team led by Michael Brines and Anthony Cerami mapped which parts of EPO carried the protective signal. They found that helix B, residues 58 to 82, faces the watery space outside the receptor when EPO is bound, and that helix B alone protected nerve cells in the dish and tissue in live animals. They then cut it further, to an 11-amino-acid stretch made of the amino acids that form the water-facing surface of helix B. That fragment protected tissue in models of ischaemic stroke and kidney ischaemia-reperfusion, sped wound healing and improved memory in rodents, and, as intended, did not stimulate red blood cell production in the dish or in animals ^[1]. That fragment is ARA-290.

Searches for the ARA-290 erythropoietin link usually land here, and the link is literal: the peptide is a fragment of the hormone, not a mimic of it. The ARA-290 neuropathy research described below is the only part of the programme that reached a reasonably sized trial. The name is written several ways. ARA-290, ARA 290 and ARA290 are the same thing; cibinetide is its international non-proprietary name; and pHBSP, short for pyroglutamate helix B surface peptide, is the name used in much of the preclinical literature ^{[1] [2]}. Our guide to what research peptides are explains what the research-use label on a vial does and does not mean. ARA-290 is often shelved next to repair-oriented peptides such as BPC-157 and thymosin beta-4 (TB-500), but it is a different kind of compound with a specific, named receptor target.

The working model is that tissue under stress puts the EPO receptor and CD131 on its surface together, and that ARA-290 binds this pairing rather than the red-cell receptor. Activating it is reported to dampen inflammatory signalling, reduce cell death and encourage repair, without the rise in haematocrit, blood pressure risk and clotting risk that limit EPO itself ^{[1] [2]}. A 2015 review by Collino and colleagues sets out the pathway and makes the case that a short-lived peptide can produce long-lasting effects by switching tissue from an injury programme to a repair programme rather than by staying in the blood ^[2].

The receptor evidence is not just correlation. In a 2011 rat and mouse study, ARA-290 relieved tactile and cold allodynia after nerve injury for as long as 15 weeks, from only a handful of doses, and the effect was completely absent in mice bred without the beta common receptor ^[3]. That knockout result is the main experimental argument that ARA-290’s benefit really does run through CD131.

A second strand of work concerns immune cells. Cibinetide has been reported to quieten innate immune cells in experimental colitis ^[4] and to reduce macrophage activation in islet transplantation models ^[5]. A third strand concerns pain signalling directly: a 2016 study reported that ARA-290 relieved pain behaviour in rats by acting on the TRPV1 channel, placing it at the junction between the immune system and pain sensing ^[6]. These are animal and cell findings, and they describe a plausible mechanism rather than a proven clinical effect.

Most claims about ARA-290 peptide benefits come from two places: the neuropathy trials described in the next section, and a wide spread of animal studies in which the peptide protected an organ under stress. The animal work covers the heart, the kidney, the eye, the gut, transplanted islets and bone, and it is consistent in direction, which is why the compound has held researchers’ attention for nearly two decades.

Heart: a 2022 study reported that a small non-haematopoietic EPO-derived peptide reduced cardiac inflammation, slowed age-related decline in heart function and prolonged healthspan in mice ^[7]. An earlier study found that chronic dosing of a small non-erythropoietic EPO sequence improved the progression of dilated cardiomyopathy after myocardial infarction in rats ^[8].

Kidney and chemotherapy toxicity: ARA-290 reduced cisplatin-induced kidney injury in rodents, with the authors attributing the effect to reduced apoptosis and inflammation ^[9], and reduced doxorubicin-related genetic damage and oxidative stress in cell studies ^[10].

Transplantation: cibinetide protected isolated human islets under stress and improved their engraftment in models relevant to intra-portal islet transplantation ^[5]. Bone: a 2021 study found that cibinetide inhibited the formation of bone-resorbing osteoclasts in the dish and increased bone mineral density in mice ^[11].

Alzheimer’s-type pathology: a 2022 study reported that early modulation of monocytes by ARA-290 slowed the progression of Alzheimer’s-like pathology in a mouse model ^[12]. None of these animal findings has been confirmed in a human trial, and none of them supports the way ARA-290 is marketed for general recovery or wellbeing.

ARA-290 is unusual among research peptides in having a real, registered clinical programme, run by Araim Pharmaceuticals. Almost all of the ARA-290 clinical trials programme concerns small nerve fibre damage, measured with corneal confocal microscopy, which counts the tiny nerve fibres in the cornea as a window on the small nerves elsewhere in the body.

The ARA-290 sarcoidosis work runs through three studies of increasing size. Sarcoidosis pilot trial, 2012: 22 patients with sarcoidosis and symptoms of small fibre neuropathy received 2 mg of ARA-290 intravenously three times a week, or placebo, for four weeks. No safety concerns were raised by clinical or laboratory assessment. The ARA-290 group improved significantly on the small fibre neuropathy screening list score compared with placebo, and on the pain and physical functioning dimensions of the SF-36 quality-of-life questionnaire. Pain and fatigue scores improved in both groups equally, and depressive symptom scores did not change ^[13].

Sarcoidosis, 2013: a blinded placebo-controlled trial gave 28 days of daily subcutaneous ARA-290 to patients with documented small nerve fibre loss and damage. Neuropathic symptoms improved, and so did corneal small nerve fibre density, cutaneous temperature sensitivity and distance walked in a six-minute walk test ^[14].

Sarcoidosis phase 2b, 2017: this is the largest published trial, 64 people with sarcoid-associated small nerve fibre loss and neuropathic pain, randomised to cibinetide 1, 4 or 8 mg per day or placebo for 28 days. The placebo-corrected change in corneal nerve fibre area at day 28 was 109 µm² in the 1 mg group, 697 µm² in the 4 mg group, which was statistically significant, and 431 µm² in the 8 mg group, which was not. Regenerating skin nerve fibres increased in the 4 mg group. Pain improved significantly in every group including placebo, and the placebo-corrected fall in pain intensity among people with moderate to severe pain did not reach significance ^[15]. The middle dose outperforming the top dose, and pain improving on placebo, are both important caveats.

Type 2 diabetes, 2015: in a phase 2 study, subjects self-administered 4 mg of ARA-290 or placebo subcutaneously each day for 28 days and were followed for a further month. No safety issues were identified. HbA1c and lipid profiles improved across the 56-day observation period, neuropathic symptoms improved significantly on the PainDetect questionnaire, and the subset with the most reduced corneal nerve fibre density showed an increase in that measure while placebo did not ^[16]. The registry entry for a related ARA-290 study in prediabetes and type 2 diabetes lists 24 participants and its status is not recorded as completed ^[21].

Diabetic macular oedema, 2020: nine patients in Belfast self-administered cibinetide 4 mg per day subcutaneously for 12 weeks and eight completed. There was no improvement in visual acuity, central retinal thickness, central retinal sensitivity or tear production. Scores on a vision-related quality-of-life questionnaire improved, and some individual participants improved on retinal thickness, tear production, diabetic control and albuminuria. No serious adverse reactions and no anti-cibinetide antibodies were seen ^[17]. The registry entry for this study records it as terminated with nine participants enrolled ^[22].

Depression model, 2015: ARA290 was tested in healthy volunteers in a neuropsychological model used to detect antidepressant activity ^[18]; the registry entry lists 36 participants in a phase 1/2 study ^[23]. Taken together, the human record is a set of small, mostly positive but not decisive phase 2 studies in neuropathy, plus two negative or inconclusive studies in the eye and in mood. There is no phase 3 trial and no approval.

Every published human trial used a 28-day or 12-week course and measured outcomes at the end of it ^{[13] [14] [15] [16] [17]}. The nerve fibre changes in the sarcoidosis trials were measured at day 28, and the metabolic changes in the type 2 diabetes trial persisted through a further month after dosing stopped ^[16]. The animal pain work is the source of the claim that effects outlast the peptide: five doses over the first two weeks after nerve injury relieved allodynia in rats for up to 15 weeks ^[3].

That pattern is a reason to be sceptical of same-week reports online. ARA-290 is a small peptide that is broken down quickly in blood by exopeptidases, with one main metabolite identified in vitro ^[19], so anything felt within hours is not explained by the published pharmacology.

The following figures describe what published studies administered under medical supervision. They are a record of the research, not recommendations, and no dose of ARA-290 has been approved for any use. In the sarcoidosis pilot, 2 mg was given intravenously three times weekly for four weeks ^[13]. In the phase 2b sarcoidosis trial, 1, 4 and 8 mg per day were given subcutaneously for 28 days, and 4 mg produced the only significant nerve fibre result while 8 mg did not ^[15]. In the type 2 diabetes trial and the diabetic macular oedema study, participants self-administered 4 mg per day subcutaneously, for 28 days and 12 weeks respectively ^{[16] [17]}.

Animal doses do not translate directly: the rat neuropathy work used 30 µg/kg by intraperitoneal injection, five doses at two-day intervals and then weekly ^[3]. If you are converting between a vial’s stated contents and a concentration, our peptide calculator and the ARA-290 calculator page do the arithmetic, but the arithmetic is the easy part; the dose itself has no settled answer outside a trial protocol.

Human trials used intravenous infusion in the earliest sarcoidosis study ^[13] and daily subcutaneous injection in every later one ^{[14] [15] [16] [17]}. Research suppliers sell ARA-290 as a freeze-dried powder for reconstitution. We found no published human study of oral, nasal or topical ARA-290, and no published pharmacokinetic study in people that would let anyone reason about an alternative route.

One practical point from the diabetic macular oedema trial: no antibodies against cibinetide were detected after 12 weeks of daily subcutaneous dosing ^[17]. Immunogenicity is a standard worry with injected peptides, so a negative antibody result in a supervised trial using pharmaceutical-grade material is worth noting, though it says nothing about material of unknown purity.

In the published trials, ARA-290 was reported as raising no safety concerns on clinical or laboratory assessment in sarcoidosis ^{[13] [14] [15]}, no potential safety issues in type 2 diabetes ^[16], and no serious adverse events or reactions in diabetic macular oedema ^[17]. These are short courses in a total of roughly 160 supervised participants across all the trials, which is far too few people and far too little time to describe a side effect profile.

The main theoretical reassurance is that ARA-290 was designed not to stimulate red blood cell production, and was shown not to do so in cells and animals ^[1]. That removes the best-known hazards of EPO itself, which are a rising haematocrit, thicker blood and clotting. It does not remove other risks. ARA-290 acts on innate immune cells ^{[4] [12]}, and deliberately damping inflammation and cell death is not automatically benign: the same signalling that protects a stressed cell can, in principle, protect a cell that should have died. No study has examined long-term or repeated ARA-290 use in people, cancer risk, fertility or use in pregnancy.

Nothing about ARA-290 supports use for muscle growth or athletic performance. We found no study of ARA-290 and muscle mass, strength or body composition, and the one place it reliably appears in the sports literature is in methods for catching it in doping control ^{[19] [20]}.

ARA-290 is not an approved medicine in the UK, US, EU, Canada, Australia or New Zealand as far as we are aware. Development has been conducted by Araim Pharmaceuticals, whose staff are authors on most of the clinical papers and declare stock ownership in the company ^{[15] [17]}. The furthest the programme has reached publicly is phase 2.

In sport, ARA-290 is treated as a prohibited peptide. A 2017 study from the Cologne anti-doping laboratory characterised the in vitro metabolism of ARA-290 explicitly as one of several “prohibited peptides” needing a detection method, and identified its main metabolite ^[19]; an earlier method paper included it among small peptides screened for in urine by direct injection ^[20]. Anyone subject to testing should treat ARA-290 as a banned substance and check the current WADA Prohibited List themselves.

Rules on buying, importing and holding research peptides differ by country. See our legal status overview and the pages for the UK, the US and Europe. Enforcement of the research-use framing has been tightening, as our coverage of the FDA advisory committee on compounded peptides describes.

ARA-290 is supplied as a lyophilised powder. Freeze-dried peptides are generally kept cold, dry and out of the light, and solutions once reconstituted are refrigerated and used within a limited window. See how to store peptides and our guide to bacteriostatic water for what is actually known about reconstitution and shelf life.

ARA-290 is short, at 11 amino acids, which makes it easier to synthesise than most peptides on this site, and it has a distinctive feature worth checking: the sequence begins with a pyroglutamate residue, which is why the preclinical name is pyroglutamate helix B surface peptide ^{[1] [2]}. A certificate of analysis should show a measured mass close to 1257 g/mol, and a mass 17 or 18 units out suggests the wrong end group rather than the right peptide.

Compare ARA-290 prices across the suppliers we track, including listings in the UK, the US and Canada. Our guide to how to read a peptide COA explains which numbers on a certificate matter, third-party peptide testing explains what independent testing does and does not prove, and how to spot a fake peptide supplier covers the warning signs. The stores that publish independent results are listed under third-party tested suppliers. Prices vary widely for reasons we set out in peptide prices explained.