Peptide Schedule
ARA-29011 residuesQEQLERALNSSEach bubble = one amino acid. Size = residue mass. Color = chemical class.ARA-290
Benefits
About ARA-290
ARA-290 (cibinetide) is a synthetic 11-amino-acid peptide derived from the three-dimensional structure of erythropoietin (EPO). It selectively activates the innate repair receptor (IRR), a heterodimer of the EPO receptor and CD131 (beta common receptor), triggering anti-inflammatory, neuroprotective, and tissue-repair signaling cascades. Unlike EPO, ARA-290 does not stimulate erythropoiesis (red blood cell production), eliminating risks of polycythemia and thrombosis. Phase 2 clinical trials have demonstrated nerve fiber regeneration and pain reduction in sarcoidosis-associated small fiber neuropathy, as well as improved metabolic control and neuropathic symptoms in type 2 diabetes.
Who Should Consider ARA-290
- Individuals with sarcoidosis-associated small fiber neuropathy
- Type 2 diabetes patients with peripheral neuropathic symptoms
- People with chronic neuropathic pain seeking non-opioid alternatives
- Patients with inflammatory tissue damage requiring nerve repair support
- Individuals with diabetic macular edema (early clinical evidence)
- Those recovering from nerve injuries with small fiber involvement
How ARA-290 Works
ARA-290 mimics the helix B surface domain of erythropoietin and selectively binds the innate repair receptor (IRR), a heterodimer of EPO receptor and CD131 (beta common receptor). IRR activation initiates anti-apoptotic signaling via the JAK2/STAT5 and PI3K/Akt pathways, suppresses pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta), and inhibits NF-kB-mediated cell death signals. In peripheral nerves, this promotes Schwann cell survival and small nerve fiber regeneration. ARA-290 also modulates TRPV1 channels, reducing nociceptive signaling in neuropathic pain. Critically, it does not activate the homodimeric EPO receptor responsible for erythropoiesis, avoiding red blood cell overproduction.
What to Expect
IRR signaling pathways activated. Anti-inflammatory cytokine modulation begins. No visible changes expected yet. Some patients report mild reduction in neuropathic pain intensity.
Measurable reduction in neuropathic pain scores observed in clinical trials. Anti-inflammatory effects established. Early nerve fiber regenerative processes underway at the cellular level.
End of standard clinical trial cycle. Corneal nerve fiber density increases documented (approximately 23% in the 4 mg group). Meaningful pain reduction in patients with moderate to severe baseline pain. Improved functional activity correlated with nerve fiber regeneration.
Nerve fiber regeneration effects may persist beyond the dosing period due to structural repair. Assess pain levels and nerve function. Consider repeating cycle after 2-week washout if further improvement is needed.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 1mg | Daily |
| Moderate | 2mg | Daily |
| Aggressive | 4mg | Daily |
Note: ARA-290 (cibinetide) is an 11-amino-acid peptide engineered from the helix B surface of erythropoietin. It selectively activates the innate repair receptor (IRR) without stimulating red blood cell production. Dose on clinical trial data: 1-4 mg SC daily for 28 days.
How to Inject ARA-290
Inject subcutaneously, typically into the abdomen or thigh. Clinical trials administered 1-4 mg SC once daily. Rotate injection sites to minimize local reactions. No requirement to inject near the affected area — ARA-290 acts systemically via the innate repair receptor.
Cycling Protocol
Clinical trials used daily SC injections for 28 days (4 weeks). Follow with a 2-week washout before repeating. Assess nerve function and pain scores between cycles.
Pharmacokinetics
Source: Human PK: plasma t1/2 ~20 minutes after 4 mg SC (Brines et al., Mol Med 2015, PMID 25569804). Peak plasma ~3 ng/mL. Rapid clearance, but downstream IRR-mediated gene expression changes persist for hours.
Loading the interactive decay curve.
Side Effects
Well-tolerated in Phase 2 trials. Mild injection site reactions (redness, soreness) are the most commonly reported adverse event. Transient headache, mild dizziness, and occasional nausea have been noted at low frequency. No significant hematological or biochemical changes observed.
Contraindications
- Pregnancy or breastfeeding — no reproductive or developmental safety data available
- Active malignancy — theoretical concern given tissue-repair and anti-apoptotic signaling
- Concurrent EPO or erythropoiesis-stimulating agent therapy — overlapping receptor pathways may cause unpredictable effects
- Known hypersensitivity to cibinetide or any excipient in the formulation
- Severe hepatic impairment — mild liver enzyme elevations reported; monitor closely in pre-existing liver disease
- Children and adolescents — no pediatric safety data available
Drug Interactions
- Erythropoietin (EPO) and erythropoiesis-stimulating agents — both target EPO receptor subunits; concurrent use may cause excessive or unpredictable receptor activation
- Strong immunosuppressants (tacrolimus, cyclosporine, biologics) — additive immune modulation effects; increased monitoring recommended
- Anti-VEGF therapies (bevacizumab, ranibizumab) — may oppose tissue-repair and angiogenic components of IRR signaling
- Anticoagulants (warfarin, heparin, DOACs) — theoretical concern given tissue repair pathway modulation; monitor coagulation parameters
Storage & Stability
Molecular Profile
Related Peptides
References
- Safety and Efficacy of ARA 290 in Sarcoidosis Patients with Symptoms of Small Fiber Neuropathy (Heij et al., Mol Med 2012)PubMed 22952059
- ARA 290 Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes (Brines et al., Mol Med 2015)PubMed 25569804
- Cibinetide Improves Corneal Nerve Fiber Abundance in Sarcoidosis-Associated Small Nerve Fiber Loss (Dahan et al., IOVS 2017)PubMed 28475704
- Erythropoietin-derived tissue-protective peptides: molecular basis and clinical application (Brines & Cerami, JCI 2004)Review
- Study of Efficacy of ARA 290 on Corneal Nerve Fiber Morphology in Sarcoidosis (NCT02039687)Clinical Trial
- ARA 290 Relieves Pathophysiological Pain by Targeting TRPV1 Channel (Peptides 2016)PubMed 26860612