ARA-290 vs Retinalamin

Non-hematopoietic EPO analogue; activates innate repair receptor (IRR/EPOR/CD131 complex) without erythropoietic effects; promotes tissue repair and nerve healing

ARA 290 (cibinetide) is a synthetic 11-amino-acid peptide derived from the helix B region of erythropoietin (EPO), engineered to activate the innate repair receptor (IRR) — a tissue-protective heteroreceptor complex comprising the EPO receptor and the β-common receptor (CD131) — without engaging the classical erythropoietic EpoR homodimer, thereby separating EPO's tissue-protective signaling from its hematopoietic effects. By selectively engaging the IRR rather than the erythropoietic receptor, cibinetide activates anti-inflammatory and anti-apoptotic intracellular pathways in neurons, endothelium, and other metabolically active tissues without causing erythrocytosis, hypertension, or thrombosis, making it a candidate for neuropathy and inflammatory tissue injury contexts. Randomized, double-blind Phase 2 clinical trials have demonstrated that cibinetide improves metabolic control and neuropathic symptom scores in patients with type 2 diabetes, and a separate study demonstrated improved corneal nerve fiber abundance in patients with sarcoidosis-associated small fiber neuropathy — providing human proof-of-concept for both diabetic and inflammatory peripheral neuropathy applications. Cibinetide (ARA 290) is an investigational compound that has not received FDA approval for any indication; Phase 2 data supports further investigation in peripheral neuropathies, but no Phase 3 completion or regulatory filing has occurred as of 2025.

Polypeptide bioregulator from bovine retina; normalizes retinal pigment epithelial and photoreceptor cell function; reduces oxidative damage in retinal tissue

Retinalamin is a polypeptide bioregulator preparation derived from retinal tissue, classified as a Khavinson-class agent investigated for neuroprotective and anti-aging effects in photoreceptors and retinal ganglion cells, proposed to support visual function by modulating gene expression and cellular homeostasis in aging retinal tissue. Like other Khavinson bioregulator preparations, retinalamin is proposed to exert tissue-specific regulatory effects through intracellular transport of ultrashort active peptide components via amino acid carrier mechanisms, modulating transcriptional activity in retinal pigment epithelium and photoreceptor cells under degenerative or age-related stress conditions. Published research on Khavinson-class ultrashort peptides has characterized intracellular transport mechanisms via POT and LAT carriers and neuroepigenetic regulatory actions in aging neural tissue, providing the class-level mechanistic framework within which retinalamin's retinal effects are proposed. Retinalamin has no FDA approval; it is used as a clinical preparation in Russia and Eastern Europe for degenerative retinal conditions, and its evidence base derives from Russian-origin preclinical and observational studies that have not been independently replicated in Western-indexed clinical literature.