Ara 290 (Cibinetide): Research Overview

What is Ara 290?

Ara 290 is an engineered 11-amino acid peptide activating the Innate Repair Receptor (IRR) to provide tissue-protective effects without red blood cell stimulation. Has FDA Orphan Drug status.

What is Ara 290 researched for?

• 23% increase in corneal nerve fiber area with sustained pain improvement.
• Nerve regeneration and metabolic improvements in Type 2 diabetes patients.
• Crosses blood-brain barrier for stroke and TBI neuroprotection.
• Improves epithelialization and angiogenesis via VEGF upregulation.
• Reduces infarct size in myocardial infarction models.
• Maintains cardiac function in aging models.
• Reduces TNF-α, IL-6, and IL-12 production.
• Reduces colitis severity in animal models.
• Improves graft survival and reduces rejection.

How does Ara 290 work?

Activates IRR through EPOR/β-common receptor complex, triggering tissue-protective signaling without erythropoietic effects.

Reported targets: EPOR, Innate Repair receptor

References

1. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain

   Culver DA, Dahan A, Bajorunas D, et al. · Investigative ophthalmology & visual science · 2017

   Phase 2b trial, 64 subjects with sarcoid neuropathy, 1-8mg SC daily for 28 days. Cibinetide significantly increased corneal and skin small nerve fiber abundance, consistent with disease-modifying effect. 23% increase in corneal nerve fiber area at 4mg dose.

   Early human study · PMID 28475703

2. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes

   Brines M, Dunne AN, van Velzen M, et al. · Molecular medicine (Cambridge, Mass.) · 2015

   Phase 2 trial, 4mg SC daily for 28 days in T2DM patients. Improvement in HbA1c and lipid profiles sustained 4 weeks post-dosing. Neuropathic symptoms significantly improved. Corneal nerve fiber density increased.

   Controlled clinical trial · PMID 25387363

3. A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema

   Lois N, Gardner E, McFarland M, et al. · Journal of clinical medicine · 2020

   9 patients, 4mg SC daily for 12 weeks. No serious adverse events. Improvement in NEI VFQ-25 composite quality of life scores. Some participants showed improvements in CRT, tear production, diabetic control, and albuminuria.

   Controlled clinical trial · PMID 32674280

4. A Small Nonerythropoietic Helix B Surface Peptide Based Upon Erythropoietin Structure Is Cardioprotective Against Ischemic Myocardial Damage Brines M, Patel NSA, Villa P, et al. Proceedings of the National Academy of

   Sciences · 2008

   Engineered helix B surface peptide (pHBSP/ARA-290) from EPO structure. Increased reactive oxygen species threshold for mitochondrial permeability transition by 40%. Reduced ischemic myocardial infarct size equivalent to EPO without erythropoietic effects.

5. Neuroprotection with an erythropoietin mimetic peptide (pHBSP) in a model of mild traumatic brain injury complicated by hemorrhagic shock

   Robertson CS, Cherian L, Shah M, et al. · Journal of neurotrauma · 2012

   pHBSP reduced contusion volume from 20.8mm3 (control) to 5.9mm3. Improved cerebral blood flow recovery and beam-walking performance. Neuroprotective effects similar to EPO without thrombotic risk.

   PMID 21545288

6. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin

   Brines M, Patel NS, Villa P, et al. · Proceedings of the National Academy of Sciences of the United States of America · 2008

   PMID 18676614

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