ARA-290
Also known as: ARA 290, ARA290, cibinetide, pHBSP
Evidence Snapshot
6 early human studies; mixed endpoints
2 papers, including receptor-model uncertainty
4 dated records: completed, terminated, and unknown
Exploratory signals; durable efficacy not established
Key Takeaways
- ARA-290 (cibinetide) is an investigational EPO-derived peptide designed for non-erythropoietic tissue-protection research.
- Early sarcoidosis studies report small-fiber nerve and symptom signals, but surrogate improvements and statistically nonsignificant pain findings must not be conflated.
- The healthy-volunteer study did not improve mood; the small diabetic macular edema study did not improve mean ocular endpoints.
- The EPOR/CD131 innate-repair-receptor model remains debated at the direct molecular-interaction level.
- Trial registry status is shown separately from published outcomes: one record is terminated for drug supply expiry, and another has an unknown current status.
- Every reviewed publication and registry summary is connected to the ARA-290 compound in the site article system.
ARA-290 is not erythropoietin
Cibinetide is an engineered 11-amino-acid peptide derived from the helix-B surface of erythropoietin, not full-length EPO and not a red-cell-stimulating substitute. Early human investigation is not proof of broad clinical benefit. This monograph is educational, with no treatment or personal-use protocol.
Table of Contents
1.Overview & Molecular Identity
ARA-290, also called cibinetide, is an 11-amino-acid peptide engineered to mimic a tissue-protective surface of erythropoietin rather than its hematopoietic action. It has been studied in peripheral nerve injury models and early human investigations of sarcoidosis-associated small-fiber neuropathy, diabetes-associated neuropathy, emotional processing, and diabetic macular edema.
These are different research populations and endpoints. A result in one setting cannot be generalized to another. The site classifies the compound as having human clinical research, which describes the existence of studies, not high-certainty efficacy. Related research goals identify scientific context, not treatment indications.
2.Mechanism of Action & Receptor Uncertainty
A frequently proposed model involves the innate repair receptor, described as an erythropoietin-receptor (EPOR) and beta-common receptor (CD131) signaling system. Preclinical work reports anti-inflammatory and tissue-protective effects distinct from red-cell stimulation.
Swartjes et al., 2011 observed anti-allodynia activity in rats and wild-type mice, but not in beta-common receptor knockout mice. This supports a functional role for that receptor in the animal model.
However, the 2018 biophysical study did not detect a specific direct interaction between the extracellular EPOR and beta-common receptor regions in the presence or absence of EPO or ARA-290. Functional dependence and physical receptor assembly are different questions. A direct EPOR/CD131 complex should not be presented as conclusively established.
Anti-inflammatory, neuroprotective, and repair terminology describes research hypotheses and observations, not a guarantee of clinical benefit.
3.Human Research Evidence: Positive, Mixed & Null Findings
Sarcoidosis-associated small-fiber neuropathy
- Randomized pilot, 2012: 22 participants. The small-fiber neuropathy screening score improved more with ARA-290, but pain and fatigue scores improved equivalently in both groups; depressive symptoms did not change.
- Blinded placebo-controlled study, 2013: reported symptom, corneal nerve-fiber density, temperature-sensitivity, and walking-capacity signals after a short treatment period. These require confirmation.
- Randomized phase 2b study, 2017: 64 participants. A significant primary corneal nerve-fiber-area increase occurred in one of three active groups (P=0.012). The reported placebo-corrected pain comparison was not statistically significant (P=0.157). A nerve-imaging surrogate is not equivalent to confirmed pain relief.
Type 2 diabetes and painful neuropathy
The phase 2 publication reported metabolic and neuropathic-symptom signals during a 56-day observation period, with a corneal-fiber finding in a subgroup with reduced baseline density. Short-term and subgroup findings do not establish durable disease modification. Do not assume this paper is the same trial as NCT01933529.
Emotional processing: no demonstrated mood benefit
The 36-person healthy-volunteer randomized experiment found mixed neural and attentional changes but no effect on mood or affective symptoms. The authors did not find an unequivocal antidepressant-like profile. Healthy-volunteer processing measures do not establish depression-treatment efficacy.
Diabetic macular edema: null mean ocular endpoints
The open-label nine-patient study had eight completers and found no mean improvement in visual acuity, central retinal thickness, retinal sensitivity, or tear production. A visual-function questionnaire and some individual exploratory measures improved. With no control group and a tiny sample, those signals do not override the null ocular findings.
4.Registered Clinical Trials & Administrative Status
| Registry ID | Research context | Status checked October 15, 2026 | Results posted |
|---|---|---|---|
| NCT02039687 | Sarcoidosis neuropathy; 64 actual participants | COMPLETED | Yes |
| NCT02070783 | Healthy-volunteer emotional processing; 36 actual participants | COMPLETED | No registry results; publication available |
| NCT06626971 | Diabetic macular oedema; 9 actual participants | TERMINATED: expired study drug; no replacement | No registry results; publication available |
| NCT01933529 | Prediabetes / drug-naive type 2 diabetes; 24 estimated participants | UNKNOWN; last known ACTIVE_NOT_RECRUITING | No |
Read the connected registry summaries and their official source links:
- NCT02039687: sarcoidosis phase 2.
- NCT02070783: emotional-processing experiment.
- NCT06626971: terminated diabetic macular oedema study.
- NCT01933529: unknown-status metabolic study.
Registry records are not standalone efficacy publications. Completed does not mean successful. No posted results does not prove treatment failure. UNKNOWN is not a confirmation of continuing recruitment. Drug-expiry termination is not proof of toxicity. These are dated snapshots, not automatic live updates.
The macular edema publication also identifies EudraCT 2015-001940-12 and ISRCTN16962255. These identifiers describe the same research context and must not be counted as additional independent efficacy studies.
5.Preclinical Evidence & Translational Limits
The 2011 animal neuropathy study supports anti-allodynia activity and receptor dependence in experimental nerve injury. Rodent behavioral endpoints cannot establish a human treatment protocol.
The 2018 mechanistic study supplies important counter-evidence to a simplified receptor-assembly explanation. Including such uncertainty helps separate reproducible observations from proposed mechanisms.
Neither basic-science result establishes human dose equivalence, durable clinical efficacy, or long-term safety. This monograph is a curated review of eight publications, not a comprehensive systematic review of all ARA-290 literature.
6.Pharmacology, Handling & Analytical Gaps
The reviewed sources identify a small engineered peptide rather than a full-length erythropoietin protein. Short-term research administration is documented in the original clinical publications, but this monograph intentionally provides no personal dosing, injection, or reconstitution instructions.
No standardized clinical half-life, oral bioavailability, shelf life, storage temperature, or personal-use preparation protocol is established by this curated evidence set. Unverified numerical values are therefore not supplied. Laboratory handling should follow the material-specific safety documentation and a validated institutional protocol.
A material label or purity claim does not establish identity, sterility, clinical suitability, or equivalence to the investigational preparation used in trials. No supplier or commercial source is endorsed here.
7.Safety, Null Outcomes & Research Limitations
Some short clinical studies reported no identified safety concerns or no serious adverse events. Absence of a signal in a small, short study is not evidence of long-term safety. Rare events, immunogenicity, interactions, and safety in excluded populations cannot be reliably estimated from these reports.
Important limitations include small samples, short observation windows, surrogate endpoints, subgroup analyses, overlapping development programs, and an uncontrolled macular edema study. Independence of cohorts and sponsors should be checked in the full publications before combining results.
The evidence includes a nonsignificant pain comparison, null mood effects, null mean ocular outcomes, and a terminated registry entry. These are shown alongside positive findings rather than omitted. The terminated trial reports a drug-supply problem, not an established safety failure.
Research education only. Not medical advice, not a recommendation for human use, and not a replacement for professional clinical care. Early study participation and published research do not themselves constitute regulatory approval or an established standard of care.
8.Evidence Quality & Open Research Questions
The existence of randomized human studies raises the evidence level above a solely theoretical compound, but certainty about durable benefit remains limited. The key unanswered questions include:
- Can independent, adequately powered trials reproduce patient-important symptom and function improvements?
- How well do corneal nerve-fiber changes predict durable neuropathy outcomes?
- Is there a consistent exposure-response relationship across different indications?
- What is the molecular basis of the proposed repair-signaling pathway?
- What are the longer-term safety and interaction profiles?
- Will unknown-status trials be updated and unpublished registry results made available?
The linked evidence list below uses real Article records associated with the compound, so evidence badges, reverse article links, research-goal connections, and the Compound Command Center share the same underlying relationships.
9.Frequently Asked Questions
10.PubMed References
- 1.Cheung Tung Shing KS, Broughton SE, Nero TL, et al. EPO does not promote interaction between the erythropoietin and beta-common receptors. Scientific reports. 2018 Aug 20. DOI: 10.1038/s41598-018-29865-x. PMID: 30127368.PMID: 30127368
- 2.Swartjes M, Morariu A, Niesters M, et al. ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain: an experimental study in rats and β-common receptor knockout mice. Anesthesiology. 2011 Nov. DOI: 10.1097/ALN.0b013e31822fcefd. PMID: 21873879.PMID: 21873879
- 3.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. Journal of clinical medicine. 2020 Jul 14. DOI: 10.3390/jcm9072225. PMID: 32674280.PMID: 32674280
- 4.Cerit H, Veer IM, Dahan A, et al. Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2015 Dec. DOI: 10.1016/j.euroneuro.2015.09.005. PMID: 26431906.PMID: 26431906
- 5.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. Investigative ophthalmology & visual science. 2017 May 1. DOI: 10.1167/iovs.16-21291. PMID: 28475703.PMID: 28475703
- 6.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. Molecular medicine (Cambridge, Mass.). 2015 Mar 13. DOI: 10.2119/molmed.2014.00215. PMID: 25387363.PMID: 25387363
- 7.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. Molecular medicine (Cambridge, Mass.). 2013 Nov 8. DOI: 10.2119/molmed.2013.00122. PMID: 24136731.PMID: 24136731
- 8.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. Molecular medicine (Cambridge, Mass.). 2012 Nov 15. DOI: 10.2119/molmed.2012.00332. PMID: 23168581.PMID: 23168581
Research Goals
Linked Research Evidence (12)
Published studies and registry summaries. Trial registration alone is not evidence of efficacy.
NCT06626971 — The Use of ARA290 for the Treatment of Diabetic Macular Oedema
NCT06626971: TERMINATED; 9 participants (actual). The registry reports termination because the study drug expired and no replacement was available, not because toxicity was established. The nine-participant macular edema publication reports null mean ocular endpoints and separate exploratory signals. No tabular results are posted in this registry record.
A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema.
A nine-patient open-label diabetic macular edema study found no mean improvement in visual acuity, retinal thickness, retinal sensitivity, or tear production.
EPO does not promote interaction between the erythropoietin and beta-common receptors.
Biophysical experiments did not detect a specific direct interaction between the extracellular EPOR and beta-common receptor domains, including in the presence of ARA-290.
Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain.
A 64-subject randomized phase 2b trial improved a corneal nerve-fiber surrogate in one dose group, but the reported placebo-corrected pain difference was not statistically significant.
NCT02039687 — Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis
NCT02039687: COMPLETED; 64 participants (actual). This completed 64-participant randomized phase 2 trial has registry results posted. The published corneal nerve-fiber surrogate signal must be distinguished from the nonsignificant reported placebo-corrected pain comparison.
NCT01933529 — ARA290 in T2D (Effects of ARA 290, an Erythropoietin Analogue) in Prediabetes and Type 2 Diabetes)
NCT01933529: UNKNOWN; 24 participants (estimated). The current registry status is UNKNOWN. ACTIVE_NOT_RECRUITING is only the last known status, not confirmation that the trial is still active. Enrollment is estimated, not actual. No registry results are posted. Do not automatically attach the separate painful-diabetic-neuropathy paper (PMID 25387363) to this prediabetes/drug-naive diabetes trial.
ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.
An early controlled phase 2 study in type 2 diabetes with painful neuropathy reported metabolic and neuropathic symptom signals over 56 days, with subgroup nerve-fiber findings.
NCT02070783 — Cognitive and Neural Effects of ARA290
NCT02070783: COMPLETED; 36 participants (actual). The registry lists depression as a condition, but the experiment enrolled healthy volunteers. Its derived publication, PMID 26431906, reports no effect on mood and mixed emotional-processing effects; it is not evidence of antidepressant treatment efficacy. No tabular results are posted in the registry record.
ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.
A blinded placebo-controlled sarcoidosis study reported improved neuropathic symptoms and corneal nerve-fiber density after 28 days; the findings remain exploratory.
Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study.
A 22-patient randomized sarcoidosis pilot reported improvement in the small-fiber neuropathy screening score, but pain and fatigue scores improved similarly in both groups.
Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action.
A 36-person randomized healthy-volunteer experiment found mixed emotional-processing effects and no effect on mood or affective symptoms.
ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain: an experimental study in rats and β-common receptor knockout mice.
Rat and receptor-knockout mouse experiments found anti-allodynia effects that depended on the beta-common receptor, supporting a preclinical mechanism rather than human efficacy.