ARA-290

In simple words

ARA-290 (cibinetide) is a peptide derived from the hormone erythropoietin but without its effect on blood. It was studied in two clinical trials in small-nerve damage, where it improved the condition of nerve fibers and reduced symptoms.

What this molecule is

A linear 11-aa peptide derived from the tertiary structure of EPO. Binds to the EPOR/βcR heterodimer — not to the EPOR/EPOR homodimer. ~1258 Da.

Why it is studied

2 RCTs in sarcoidosis-associated small fiber neuropathy: ↑corneal nerve fiber density, ↓neuropathic symptoms. Level A. No erythropoietic side effects. A rare combination — two full-fledged RCTs in neuropathy.

How it works

EPOR/βcR heterodimer → JAK2/STAT3 → ↓neuronal apoptosis, ↓neuroinflammation (↓TNF-α, IL-6), ↑regeneration of small nerve fibers. Unlike full-length EPO — no activation of the EPOR/EPOR homodimer → no erythrocytosis.

Doses used in studies

Clinical studies used 2-4 mg/day SC for 28 days. Longer use is possible.

Combined with in studies

• NAD+/NMN — neuroenergetics
• Dihexa — HGF + EPOR — different neuroprotection receptors
• ALA — complementary for neuropathy

Level of evidence

Level A-B Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. 2 RCTs in neuropathy. A rarity for a little-known peptide.

Important to know

⚠️ Small samples n=22-35. Sarcoidosis neuropathy only. Phase III has not started. Araim Pharmaceuticals halted the program. Research only.

Studies in PubMed

1. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. (Mol Med, 2012)
2. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain. (Invest Ophthalmol Vis Sci, 2017)
3. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. (Mol Med, 2013)
4. Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke. (CNS Neurosci Ther, 2024)
5. A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan. (Front Cardiovasc Med, 2022)
6. ARA 290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response. (Mol Pain, 2014)