ARA-290

Overview

ARA-290 (Cibinetide) is a synthetic 11-amino-acid peptide derived from erythropoietin (EPO) that selectively activates the innate repair receptor (IRR) for neuroprotective and tissue repair properties without erythropoietic effects.

Mechanism of Action

ARA-290 selectively binds the innate repair receptor (IRR), a heterodimer of EPOR and CD131. Unlike EPO, it does not bind the homodimeric EPOR and does not stimulate erythropoiesis. IRR activation triggers JAK2/STAT5 and PI3K/Akt pathways, promoting anti-apoptotic gene expression, reducing proinflammatory cytokines, and supporting Schwann cell survival and axonal regeneration.

Research Summary

A Phase II RCT in sarcoidosis-associated small fiber neuropathy showed ARA-290 (4mg SubQ 3x/week for 28 days) significantly improved corneal nerve fiber density and neuropathic pain scores vs placebo (Dahan et al., Pain, 2013). A Phase II trial in type 2 diabetes neuropathy showed improved intraepidermal nerve fiber density after 8 weeks (Brines et al., Molecular Medicine, 2015).

Dosing Information

Reported Side Effects

• Injection site reactions (erythema, mild pain)
• Headache
• Mild nausea
• Upper respiratory tract symptoms

Research References

• ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density (2013)
• ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes (2015)