ARA-290

ARA-290 (Cibinetide) is a non-erythropoietic peptide derived from erythropoietin (EPO) that selectively activates the innate repair receptor (IRR) — a heterodimer of the EPO receptor and the beta common receptor. Unlike EPO itself, ARA-290 does not stimulate red blood cell production but retains the tissue-protective and anti-inflammatory properties of EPO. It is studied for neuropathic pain, small fiber neuropathy, sarcoidosis-related complications, and metabolic disorders.

— 16 mg Vial —

Reconstitute: Add 2.0 mL Phosphate Buffered Saline (PBS) → 8 mg/mL concentration. (Some people will reconstitute with 1.6 mL of PBS and .4mL of bacteriostatic water. If the pH level is off it will get cloudy.
Easy measuring: At 8 mg/mL, 1 unit = 0.01 mL = 80 mcg on a U-100 insulin syringe.
Storage: Lyophilized: refrigerate at 2–8 °C or freeze at −20 °C; reconstituted: refrigerate and use within 28 days.

Schedule: Daily subcutaneous injections for 4–8 weeks (clinical trials used 28-day protocols).
Cycle Length: 4–8 weeks standard; may extend to 16 weeks based on individual assessment.
Goal: Support tissue protection, anti-inflammatory signaling, and neuropathic symptom management via IRR activation.

Frequency: Inject once daily subcutaneously. Clinical studies used 4 mg/day as the target therapeutic dose, with no additional benefit observed at 8 mg. Starting at 2 mg for the first week allows assessment of individual tolerance.

• Reduces neuropathic pain and small fiber neuropathy symptoms
• Anti-inflammatory — reduces TNF-α, IL-6, and other pro-inflammatory cytokines
• Promotes nerve fiber regeneration and repair
• Improves insulin sensitivity in metabolic research
• Studied for sarcoidosis-associated neuropathy (Phase 2 clinical trials)
• Cardioprotective effects — reduces ischemia-reperfusion injury
• No erythropoietic effects — does not raise hematocrit or risk thrombosis
• Neuroprotective — supports neuron survival under stress conditions
• May improve corneal nerve fiber density (measurable neuropathy biomarker)

ARA-290 selectively activates the innate repair receptor (IRR), a heteromeric receptor complex formed by the EPO receptor (EPOR) and the beta common receptor (βcR). This receptor is expressed on neurons, immune cells, and endothelial cells — but not on erythroid progenitors, explaining ARA-290’s lack of erythropoietic activity. IRR activation triggers cytoprotective signaling (PI3K/Akt, STAT3) that reduces apoptosis, promotes repair, and suppresses innate immune activation. In peripheral nerves, this translates to reduced pain signaling and improved axonal regeneration.

• Injection site reactions (mild)
• Transient headache
• Nausea (generally mild)
• Fatigue in some subjects
• No significant erythropoietic or cardiovascular adverse effects in clinical trials to date

ARA-290 is generally well-tolerated in clinical trials. Injection site rotation is recommended for SubQ administration. No dose reduction is typically required for mild side effects. Clinical trials have not identified serious safety signals at research doses.

• Known hypersensitivity to EPO or EPO-derived peptides
• Pregnancy and lactation (insufficient data)
• Active hematological malignancy

• Pulman KG et al. (2014). ARA 290 in chronic painful sarcoidosis. Journal of Clinical Investigation. DOI: 10.1172/JCI73780
• Brines M et al. (2014). ARA290, an innate repair receptor ligand, reduces neuropathic pain. PLOS ONE. DOI: 10.1371/journal.pone.0064724
• Dahan A et al. (2015). ARA290 in patients with sarcoidosis and chronic pain. Pain. DOI: 10.1097/j.pain.0000000000000310