ARA-290 — Research, Dosing & Price Guide

ARA-290 (cibinetide) is an 11-amino-acid synthetic peptide derived from the three-dimensional structure of erythropoietin (EPO) that selectively activates the innate repair receptor (IRR) without stimulating erythropoiesis or increasing red blood cell counts. It possesses potent anti-inflammatory, tissue-protective, and nerve-regenerative properties, with clinical trial data demonstrating benefits for small fiber neuropathy, sarcoidosis-associated neuropathy, and diabetic complications. It represents a paradigm shift in EPO-derived therapeutics — harnessing tissue protection without blood-thickening risks.

ARA-290 binds to the innate repair receptor (IRR), a heteromeric complex formed by the EPO receptor (EPOR) and the beta-common receptor (βcR, also known as CD131). This receptor complex is distinct from the classical homodimeric EPOR that drives erythropoiesis, and it is preferentially expressed on injured, inflamed, or stressed tissues — meaning ARA-290 selectively targets damaged tissue rather than acting systemically. When ARA-290 activates the IRR, it triggers JAK2 phosphorylation and downstream activation of STAT5, PI3K-Akt, and NF-κB inhibitory pathways. The functional consequences include: suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6); inhibition of apoptosis in stressed cells via Bcl-2 upregulation and Bad phosphorylation; promotion of efferocytosis (the clearance of dead cells by macrophages); and stimulation of tissue repair processes including angiogenesis and axonal regeneration. Critically, ARA-290 has no affinity for the classical homodimeric EPOR, meaning it produces zero erythropoietic effects — no increase in hematocrit, hemoglobin, or red blood cell mass. This eliminates the thromboembolic risks associated with EPO and makes ARA-290 safe for conditions where EPO's tissue-protective effects are desired but its blood-thickening effects are dangerous.

• A Phase II clinical trial in small fiber neuropathy demonstrated significant improvement in corneal nerve fiber density (a validated surrogate for peripheral nerve regeneration) after 28 days of treatment — one of the first compounds to show objective nerve regrowth in humans.
• In sarcoidosis-associated small fiber neuropathy, ARA-290 reduced neuropathic pain scores by approximately 50% and improved autonomic function parameters.
• Clinical data in type 2 diabetic patients showed metabolic improvements including reduced HbA1c, suggesting the IRR pathway has direct metabolic benefits beyond tissue repair.
• Phase II studies demonstrated improved wound healing in diabetic foot ulcers, with treated patients showing accelerated wound closure rates compared to standard care.
• Preclinical studies showed ARA-290 reduced infarct size by 50% in a rat cardiac ischemia-reperfusion model, demonstrating potent cardioprotective effects.
• Unlike EPO, ARA-290 produced no changes in hematocrit, hemoglobin, or reticulocyte counts in any clinical study — confirming complete separation of tissue-protective and erythropoietic activities.

• Clinical trial dose for neuropathy: 4 mg subcutaneous injection, administered 3 times per week for 28 days. This is the best-characterized human dosing protocol.
• Extended neuropathy protocol: 4 mg SC three times weekly for 12 weeks, used in longer clinical studies for sustained nerve regeneration.
• Daily dosing protocol: 2–4 mg SC daily for 28 days, used in some diabetic complication studies.
• Self-administered subcutaneously in clinical trial settings — patients were trained on SC injection technique and managed dosing at home.
• For chronic conditions (neuropathy, sarcoidosis), protocols of 8–12 weeks with 3x weekly dosing have been used in extended studies.
• No food timing restrictions. Can be administered at any time of day.
• Research-grade reconstitution: add bacteriostatic water to lyophilized vial per label instructions. Typical concentration yields 2 mg per 0.5 mL injection.

Known Side Effects

• Injection site reactions — mild redness or pain at the injection site, the most commonly reported adverse event in clinical trials. Generally mild and self-limiting.
• Headache — reported by a small percentage of trial participants, typically mild.
• Mild gastrointestinal symptoms — occasional nausea reported, not dose-limiting.
• Upper respiratory tract infections — reported at similar rates in treatment and placebo groups, likely not treatment-related.
• No serious adverse events attributed to ARA-290 in any completed clinical trial.
• No hematological changes — critically, no increase in red blood cells, hemoglobin, or hematocrit, confirming safety over EPO.

Safety Profile

ARA-290 has demonstrated an excellent safety profile across multiple Phase II clinical trials involving hundreds of patients. The complete absence of erythropoietic effects eliminates the most significant risk associated with EPO-derived compounds — blood thickening and thromboembolism. No serious adverse events have been attributed to ARA-290 treatment in published trial data. Contraindications are theoretical and precautionary: active malignancy (the IRR could theoretically protect tumor cells from apoptosis, though no evidence supports this), severe immunosuppression, and pregnancy/breastfeeding. Drug interactions are not well-characterized but are expected to be minimal given the peptide's targeted mechanism. It does not affect CYP450 enzymes. Patients on anticoagulants can use ARA-290 safely (unlike EPO). The compound's selective activity on stressed/injured tissue provides an inherent safety advantage — healthy tissue with low IRR expression is largely unaffected.

Week 1: ARA-290 begins modulating the innate repair receptor in damaged tissues. Anti-inflammatory effects may produce subtle improvements in pain levels or discomfort, though nerve regeneration is not yet apparent. Weeks 2–4: Anti-inflammatory effects become more noticeable. Patients with neuropathic pain may experience meaningful reduction in symptoms. Wound healing begins to accelerate. Corneal confocal microscopy (if performed) may show early signs of nerve fiber regeneration. Weeks 5–8: Nerve regeneration becomes more measurable. Clinical trials showed significant corneal nerve fiber density increases by this point. Pain reduction continues to improve. Metabolic markers (HbA1c in diabetics) may show improvement. Weeks 9–12: Maximum benefits from extended protocols. Nerve fiber regeneration continues. Improvements in autonomic function and sensory thresholds become established. Benefits may continue to accrue for weeks after cessation as regenerated nerve fibers mature.

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