Ara 290: Research Applications
🧠 Neuropathic Pain & Small Fiber Neuropathy (SFN)
ARA-290 has been extensively studied for its ability to relieve neuropathic pain and repair small nerve fibers. In a spared nerve injury model, Swartjes et al. demonstrated a dose-dependent, long-term relief of both mechanical and cold allodynia lasting up to 20 weeks (doses: 30–60 µg/kg IP, p < 0.001 vs vehicle) coupled with suppression of spinal microglia activation. [7]
In human clinical trials (the NERVARA trial), 4 mg SC daily for 28 days produced a 14.5% increase in corneal nerve fiber area vs. a 5.3% decrease in placebo (p = 0.022), demonstrating measurable nerve regeneration. [4] The SFNSL symptom score improved by −12.2 points in the ARA-290 group vs. −3.8 in placebo (p = 0.005), and 6-Minute Walk Test distance increased by +18.7 m vs. −15.1 m in placebo (p = 0.049). [4]
🩺 Type 2 Diabetes & Metabolic Control
In Phase 2 studies involving study subjects with type 2 diabetes, ARA-290 (4 mg SC daily for 28 days) significantly improved HbA1c (−0.16% vs. −0.01% placebo, p = 0.002), with effects sustained at day 56. [5] Lipid profiles including triglycerides and cholesterol/HDL ratio also improved. PainDetect neuropathy scores improved +3.3 points vs. +1.1 in placebo (p = 0.037). [5]
In preclinical models, ARA-290 (30 µg/kg SC) ameliorated diet-induced insulin resistance in mice, reducing hepatic lipid deposition, normalizing serum glucose, and enhancing mitochondrial biogenesis in skeletal muscle. [12]
❤️ Cardiovascular Protection & Aging
Chronic ARA-290 research application (100 µg/kg IP, tri-weekly for 15 months) in aging rats mitigated the age-associated increase in left ventricular end-systolic volume by ~75% (p < 0.05), blunted ejection fraction decline by almost half (p < 0.0001), and significantly reduced blood pressure elevation (p < 0.008). [1] Treated rats showed significantly lower cardiac inflammation (CD45 leukocytes p < 0.001, CD68 monocytes p < 0.001), reduced NF-κB activity, and lower frailty index scores at 33 months of age (p < 0.001). [1]
See also: BPC-157 and TB-500 for related tissue repair research.
References
- Winicki NM, Nanavati AP, Morrell CH, et al. A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan. Front Cardiovasc Med, 9, 1096887, 2023.
- Brines M, Patel NS, Villa P, et al. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. PNAS USA, 105(31), 10925–10930, 2008.
- Swartjes M, Morariu A, Niesters M, et al. ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain. Anesthesiology, 115(5), 1084–1092, 2011.
- Dahan A, Dunne A, Swartjes M, et al. ARA 290 improves symptoms in study subjects with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med, 19(1), 334–345, 2013.
- Brines M, Dunne AN, van Velzen M, et al. ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in study subjects with Type 2 Diabetes. Mol Med, 20(1), 658–666, 2015.
- Heij L, Niesters M, Swartjes M, et al. tolerability and efficacy of ARA 290 in sarcoidosis study subjects with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med, 18(1), 1430–1436, 2012.
- Swartjes M, van Velzen M, Niesters M, et al. ARA 290 produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response. Mol Pain, 10, 13, 2014.
- McVicar CM, Hamilton R, Colhoun LM, et al. Intervention with an erythropoietin-derived peptide protects against neuroglial and vascular degeneration during diabetic retinopathy. Diabetes, 60(11), 2995–3005, 2011.
- Culver DA, Dahan A, Bajorunas D, et al. Cibinetide Improves Corneal Nerve Fiber Abundance in study subjects With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain. Invest Ophthalmol Vis Sci, 58(6), BIO52–BIO60, 2017.
- Lois N, Gardner E, McFarland M, et al. A Phase 2 Clinical Trial on the Use of Cibinetide for the investigation of Diabetic Macular Edema. J Clin Med, 9(7), 2225, 2020.
- Nairz M, Haschka D, Dichtl S, et al. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. Sci Rep, 7(1), 13012, 2017.
- Collino M, Benetti E, Rogazzo M, et al. A non-erythropoietic peptide derivative of erythropoietin decreases susceptibility to diet-induced insulin resistance in mice. Br J Pharmacol, 171(24), 5802–5815, 2014.
- Tokodai K, Brines M, Ericzon BG, et al. Improvement of Islet Allograft Function Using Cibinetide, an Innate Repair Receptor Ligand. Transplantation, 104(10), 2020.
- Kumagai-Braesch M, Cerami A, Ericzon BG, et al. Cibinetide Protects Isolated Human Islets in a Stressful Environment. Cell Transplantation, 30, 2021.
- Schmidt RE, Feng D, Wang Q, et al. Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy in Akita diabetic mouse sympathetic ganglia. Exp Neurol, 232(2), 126–135, 2011.
- Niesters M, Swartjes M, Heij L, et al. The erythropoietin analog ARA 290 for investigation of sarcoidosis-induced chronic neuropathic pain. Expert Opin Orphan Drugs, 1, 77–87, 2013.
- Pulman KG, Smith M, Mengozzi M, et al. The erythropoietin-derived peptide ARA290 reverses mechanical allodynia in the neuritis model. Neuroscience, 233, 174–183, 2013.
- Brines M. Discovery of a Master Regulator of Injury and Healing: Tipping the Outcome from Damage toward Repair. Mol Med, 20(Suppl 1), S10–S16, 2014.
- Ahmet I, Tae H, Brines M, et al. Chronic administration of small nonerythropoietic peptide of erythropoietin ameliorates postmyocardial infarction-dilated cardiomyopathy. J Pharmacol Exp Ther, 345(3), 446–456, 2013.
- Coldewey SM, Khan AI, Kapoor A, et al. Erythropoietin attenuates acute kidney dysfunction in murine experimental sepsis by activation of the β-common receptor. Kidney Int, 84(3), 482–490, 2013.
- Muller C, Yassin K, Li LS, et al. ARA290 Improves Insulin Release and Glucose Tolerance in Type 2 Diabetic Goto-Kakizaki Rats. Mol Med, 21(1), 969–978, 2016.
Related Research Questions
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