ARA-290
An investigational peptide based on a non-blood-forming region of erythropoietin, studied mainly for neuropathic pain and small-fibre neuropathy in conditions like sarcoidosis and diabetes. It has reached human trials but is not approved for any use.
Quick take
- What it is: a peptide derived from a region of erythropoietin (EPO) that activates tissue-protective signalling without EPO's blood-boosting effect.
- What people use it for: nerve-related (neuropathic) pain and small-fibre neuropathy, including in sarcoidosis and diabetes.
- What we actually know: it has reached early human trials with some promising signals, but it is not approved and the evidence remains limited.
- Status: an investigational drug; not FDA-approved or approved elsewhere.
What it is
ARA-290, also known as cibinetide, is an investigational peptide derived from a specific region of erythropoietin (EPO). EPO is best known for stimulating red-blood-cell production, but it also has separate tissue-protective and anti-inflammatory signalling roles. ARA-290 was designed to capture those protective effects without the blood-cell-boosting (and clot-risk) activity of full EPO.1
It has been studied mainly for nerve-related pain. As an investigational compound, the key point is that it has entered human research but is not an approved medicine.
How it works
ARA-290 is thought to act on the “innate repair receptor” — a tissue-protective receptor complex associated with EPO that is distinct from the classic receptor driving red-cell production. Activating this pathway is proposed to reduce inflammation and protect nerve and other tissues, which is the rationale for studying it in small-fibre neuropathy and neuropathic pain.2
By selectively targeting tissue protection rather than red-cell formation, the goal is to avoid the cardiovascular risks linked to raising EPO activity.
What the evidence shows
Laboratory and animal studies
Preclinical work supports ARA-290’s anti-inflammatory and tissue-protective actions in models of nerve injury, inflammation and metabolic disease.2 This foundation justified moving it into human testing.
Human studies
ARA-290 has reached early-phase human clinical trials, notably in sarcoidosis-related small-fibre neuropathy and in diabetic neuropathy, with some reports of improvement in pain and nerve-related measures.3 These results are encouraging but come from relatively small, early studies. The honest summary is promising early human signals that are not yet confirmed by large, definitive trials.
Dosages reported in the literature
Informational only. The figures below describe doses used in clinical trials. They are not a recommendation or a prescription. Appropriate use, if any, should be determined by a qualified healthcare professional within an appropriate clinical setting.
| Setting | Route | Reported range |
|---|---|---|
| Clinical trials | Subcutaneous | Reported around a few milligrams daily, in study-defined courses |
| Anecdotal use | Subcutaneous | Varies; not standardised or validated outside trials |
Because ARA-290 is investigational, dosing exists only in a trial context and should not be read as established for general use.
Safety & side effects
Within the trials conducted to date, ARA-290 has generally been described as well tolerated, with injection-site reactions among the reported issues.3 However, there are no long-term safety data outside controlled studies, and its full risk profile remains to be established.
As an investigational compound, any material sold outside formal trials also carries the usual concerns about identity, purity and dose accuracy.
Legal & regulatory status
ARA-290 (cibinetide) is not approved by the FDA or other regulators for any use. It is an investigational drug that has been evaluated in clinical trials but has not received marketing approval.4 Rules differ by country and change over time.
References
- Brines M, Patel NS, Villa P, Brines C, Mennini T, De Paola M, Erbayraktar Z, Erbayraktar S, Sepodes B, Thiemermann C, Ghezzi P, Yamin M, Hand CC, Xie QW, Coleman T, Cerami A. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci U S A. 2008;105(31):10925-30. [PMID 18676614, doi:10.1073/pnas.0805594105]
- Swartjes M, van Velzen M, Niesters M, Aarts L, Brines M, Dunne A, Cerami A, Dahan A. 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;10:13. [PMID 24529189, doi:10.1186/1744-8069-10-13]
- Heij L, Niesters M, Swartjes M, Hoitsma E, Drent M, Dunne A, Grutters JC, Vogels O, Brines M, Cerami A, Dahan A. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med. 2012;18(1):1430-6. PMID 23168581; DOI 10.2119/molmed.2012.00332. ALSO: 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;58(6):BIO52-BIO60. PMID 28475703; DOI 10.1167/iovs.16-21291. ALSO: 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;20(1):658-66. PMID 25387363; DOI 10.2119/molmed.2014.00215. [PMID 23168581, PMID 28475703, PMID 25387363, doi:10.2119/molmed.2012.00332]
- ClinicalTrials.gov. A Double Blind, Placebo Controlled Phase 2 Dose Ranging Study of the Effects of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis (NCT02039687). Sponsor: Araim Pharmaceuticals, Inc. U.S. National Library of Medicine. Supplemented by U.S. FDA Orphan Drug Designation for ARA 290 (cibinetide) for treatment of sarcoidosis (granted July 2016) — investigational/designation status only, not marketing approval. [clinicaltrials.gov]