ARA-290

ARA-290 (cibinetide) is an 11-amino acid peptide derived from the helix B surface of erythropoietin (EPO) that selectively activates the innate repair receptor (IRR, also called tissue-protective receptor) without stimulating the classical erythropoietin receptor responsible for red blood cell production.

This selectivity is crucial because while EPO has potent tissue-protective and anti-inflammatory properties, its erythropoietic effects cause dangerous blood thickening (polycythemia) when used for tissue protection. ARA-290 provides the beneficial tissue-protective effects without the cardiovascular risks.

The innate repair receptor is a heterodimer of EPOR and CD131 (beta common receptor) expressed on immune cells, neurons, and tissue-resident stem cells. Activation promotes an anti-inflammatory phenotype, enhances tissue repair, and provides cytoprotection through mechanisms distinct from classical EPO signaling.

Clinical research has evaluated ARA-290 for small fiber neuropathy in sarcoidosis and diabetes, where it has demonstrated improvements in nerve fiber density and neuropathic symptoms. Additional research explores its potential in chronic inflammatory conditions where tissue protection and inflammation resolution are therapeutic goals.