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ARA 290

unknown risk

Also: Cibinetide · ARA290 · ERY290

Preliminary Research Only

ARA 290 is a non-hematopoietic analog of erythropoietin engineered to activate tissue-protective but not erythropoiesis pathways. It has Orphan Drug designation for sarcoidosis-associated neuropathy and has demonstrated efficacy in diabetic neuropathy trials.

Molecular Weight
536.6 g/mol
Formula
C26H36N4O8
Common Dosing
4-8 mg subcutaneous daily (from trials)
Category
research
Last Reviewed
2025-01-15

Reported Benefits

Diabetic Neuropathy

Preliminary 15 studies

Phase 2 trial showed improved nerve fiber density and pain scores in T2DM patients.

Sarcoidosis Neuropathy

Preliminary 10 studies

Randomized trial demonstrated improved corneal nerve fiber density and pain.

Anti-inflammatory

Preliminary 8 studies

Activates anti-inflammatory innate repair receptor (IRR) complex.

Mechanism of Action

ARA 290 was engineered by removing the erythropoiesis-stimulating receptor-binding residues from erythropoietin while retaining the tissue-protective signaling domain. It activates the innate repair receptor (IRR) — a heterodimer of EPOR and beta-c — which mediates anti-inflammatory, anti-apoptotic, and neuroprotective signaling.

Key Clinical Studies

Brines M et al. (2014)

RCT · 40 diabetic patients

PubMed →

Improved corneal nerve fiber density after 28 days

Heij L et al. (2012)

Phase 2 RCT · Sarcoidosis patients

Improved corneal nerve fiber density in sarcoidosis

Overview

ARA 290 represents a clever approach to drug development: taking erythropoietin (EPO) — a well-characterized protein hormone with powerful tissue-protective properties — and engineering away the hematopoietic (red blood cell stimulating) activity while preserving the protective signaling. This eliminates EPO’s significant cardiovascular risks in non-anemic patients.

The Two Faces of Erythropoietin

Native EPO has two receptor binding sites: one that activates EPOR homodimers (causing erythropoiesis and the associated thrombosis risk), and one that activates the IRR heterodimer (tissue protection). ARA 290 selectively activates only the IRR pathway — a mechanistic refinement that took years to characterize.

Neuropathy Evidence

The diabetic and sarcoidosis neuropathy data is meaningful. Corneal confocal microscopy — measuring small nerve fiber density in the cornea as a proxy for systemic small fiber neuropathy — showed objective improvements in nerve fiber density, not just patient-reported pain scores. This objective endpoint strengthens the evidence quality.

Development Status

ARA 290 holds Orphan Drug designation for sarcoidosis neuropathy and has completed Phase 2 trials. Regulatory approval pathway remains active but uncertain as of 2025.

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Regulatory Status

Research Only

Orphan drug designation for sarcoidosis neuropathy; Phase 2 complete; no approval

Safety Profile

Side Effects

  • Injection site reactions (mild)
  • No hematopoietic effects by design

Contraindications

  • None established

Drug Interactions

  • None established

Primary Uses

NeuroprotectionDiabetic neuropathyInflammationSarcoidosis pain

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Disclaimer: This information is for educational and research purposes only. Not medical advice. Consult a qualified healthcare provider before using any compound.