ARA-290 (Cibinetide) for Neuroprotection & Pain Management — Brain
Non-hematopoietic EPO-derived peptide for nerve regeneration and neuropathic pain. Phase II complete. FDA Orphan Drug for sarcoidosis. NOT FDA-approved for general use.
Overview
ARA-290 (Cibinetide) is an 11-amino acid synthetic peptide engineered from the helix-B domain of erythropoietin (EPO). Unlike full-length EPO, it selectively activates the innate repair receptor (IRR) — a heterodimer of EPO receptor and β-common receptor (CD131) — delivering tissue-protective, anti-inflammatory, and neuroprotective effects WITHOUT stimulating red blood cell production. This eliminates the hematocrit elevation, thrombosis risk, and cardiovascular side effects associated with EPO therapy. CLINICAL STATUS: Phase II complete with positive results for small fiber neuropathy in sarcoidosis (23% corneal nerve fiber increase, significant pain reduction) and type 2 diabetes (improved HbA1c, lipids, pain). Received FDA Orphan Drug Designation for sarcoidosis-associated neuropathic pain. Phase III trials needed for approval. Currently available only as research peptide. KEY DIFFERENTIATOR: One of very few peptides showing objective nerve REGENERATION (not just symptom relief) in human clinical trials, confirmed by GAP-43+ fiber growth markers.
Indications
- Small fiber neuropathy (sarcoidosis, diabetes) - Phase II positive data
- Chronic neuropathic pain - 40% average pain reduction in clinical trials
- Nerve regeneration - confirmed GAP-43+ fiber growth in humans
- Cerebral ischemia/stroke recovery (preclinical - reduced infarct volume)
- Neurodegeneration and Alzheimer prevention (early research - modulates monocyte behavior)
- Cardiovascular aging protection (preclinical - reduced cardiac inflammation, improved mitochondrial function)
- Depression and chronic stress (preclinical - anti-inflammatory mechanism)
- Diabetic neuropathy with metabolic benefits (improved HbA1c and lipids)
Mechanism of Action
Small fiber neuropathy from sarcoidosis, diabetes, or other conditions causes progressive nerve fiber loss, chronic pain, and impaired function
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| ARA-290 (Cibinetide) | 4 mg | Once daily for 28 days | Validated in Phase II trials for neuropathy. Optimal dose (1mg appears ineffective). |
| ARA-290 (Cibinetide) | 2-4 mg | 2-3 times weekly for 6 weeks | Some protocols use 2-3x/week for extended periods. Lower doses for maintenance. |
Evidence Grade
GRADE B
Safety & Contraindications
- CRITICAL: NOT FDA-approved for any indication (investigational only)
- Phase II trials showed excellent safety - no serious adverse events
- Does NOT increase hematocrit, red blood cells, or thrombosis risk (key advantage over EPO)
- No cardiovascular or hematopoietic side effects
- Mild injection site reactions (redness, swelling, itching) - common
- Occasional headache (transient)
- Rare GI discomfort (nausea, mild fatigue)
- Rare liver enzyme elevation - monitor in pre-existing liver conditions
- Available only as research peptide - not sold through standard vendors
- No long-term safety data beyond 28-day clinical trials