ARA-290

ARA-290 exerts its effects by selectively activating the innate repair receptor (IRR), a heteromeric complex composed of EPO receptor (EPOR) and β common receptor (βcR) subunits. This specific interaction triggers a cascade of signaling events that lead to anti-inflammatory, tissue-protective, and repair-promoting effects. ARA-290 has been shown to modulate the immune response by reducing the production of pro-inflammatory cytokines and increasing the expression of anti-inflammatory mediators. Additionally, it promotes the survival and function of various cell types, including endothelial cells, cardiomyocytes, and neurons, under stress conditions.

• Neuroprotection: ARA-290 has demonstrated neuroprotective properties in models of spinal cord injury, traumatic brain injury, and ischemic stroke, reducing neuronal damage and promoting functional recovery.

• Cardioprotection: Studies have shown that ARA-290 can protect the heart from ischemia-reperfusion injury, reduce infarct size, and improve cardiac function in animal models of myocardial infarction.

• Renal protection: ARA-290 has been found to attenuate renal injury and improve kidney function in preclinical models of acute kidney injury and chronic kidney disease.

• Anti-inflammatory effects: The peptide exhibits potent anti-inflammatory properties, reducing the production of pro-inflammatory cytokines and promoting the resolution of inflammation in various tissues.

• Wound healing: ARA-290 has been shown to accelerate wound healing and promote tissue repair in animal models of skin, corneal, and intestinal injuries.

• Pain relief: Clinical studies have demonstrated that ARA-290 can effectively reduce neuropathic pain in patients with sarcoidosis and type 2 diabetes mellitus.

ARA-290 has been well-tolerated in clinical trials, with no significant side effects reported. Unlike EPO, ARA-290 does not stimulate erythropoiesis, minimizing the risk of thrombotic complications associated with increased red blood cell production. 

ARA-290 Experimental Reagent: Preparation Guidelines Important: Please read these instructions carefully before handling the ARA-290 experimental reagent.

Dissolution:

• Due to the high density of ARA-290, dissolve 12mg of the reagent in a minimum of 3ml of bacteriostatic water (BAC water).

Preparation Steps:

1. Remove the experimental reagent from storage and allow it to reach room temperature (approximately 2-3 hours).

2. Once at room temperature, add the appropriate amount of BAC water.

3. After reconstitution, keep the solution at room temperature. Do not refrigerate or refreeze.

Caution:

• Reconstituting or storing the reagent in low-temperature environments may cause cloudiness.

• Avoid exposing the reconstituted solution to cold temperatures to maintain its clarity and effectiveness.

For optimal results, please follow these guidelines closely.

ARA-290 is a promising synthetic peptide that mimics the tissue-protective and repair-promoting properties of EPO without stimulating erythropoiesis. By selectively activating the innate repair receptor, ARA-290 exerts potent anti-inflammatory, neuroprotective, cardioprotective, and renoprotective effects in various preclinical models. Clinical studies have also demonstrated its potential in reducing neuropathic pain and promoting wound healing. With its favorable safety profile and wide-ranging therapeutic potential, ARA-290 represents an exciting avenue for the development of novel treatments for a variety of conditions characterized by tissue damage and inflammation.

1. van Velzen M, Heij L, Niesters M, Cerami A, Dunne A, Dahan A, Brines M. ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig Drugs. 2014.

2. Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides. 2016.

3. Al-Onaizi MA, Thériault P, Lecordier S, Prefontaine P, Rivest S, ElAli A. Early monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression. Brain Behav Immun. 2022.

4. Brines M, Dunne AN, van Velzen M, Proto PL, Ostenson CG, Kirk RI, Petropoulos IN, Javed S, Malik RA, Cerami A, Dahan A. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med. 2015.

5. Watanabe M, Lundgren T, Saito Y, Cerami A, Brines M, Östenson CG, Kumagai-Braesch M. A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. Transplantation. 2016.

6. Mohtavinejad N, Hajiramezanali M, Akhlaghi M, Bitarafan-Rajabi A, Gholipour N. Synthesis and evaluation of 99mTc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region. Iran J Basic Med Sci. 2021.

7. Dahan A, Dunne A, Swartjes M, Proto PL, Heij L, Vogels O, van Velzen M, Sarton E, Niesters M, Tannemaat MR, Cerami A, Brines M. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med. 2013.

8. Atkins C, Wilson AM. Managing fatigue in sarcoidosis - A systematic review of the evidence. Chron Respir Dis. 2017.

9. Liu Y, Luo B, Han F, Li X, Xiong J, Jiang M, Yang X, Wu Y, Zhang Z. Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection. PLoS One. 2014.

10. Winicki NM, Nanavati AP, Morrell CH, Moen JM, Axsom JE, Krawczyk M, Petrashevskaya NN, Beyman MG, Ramirez C, Alfaras I, Mitchell SJ, Juhaszova M, Riordon DR, Wang M, Zhang J, Cerami A, Brines M, Sollott SJ, de Cabo R, Lakatta EG. A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan. Front Cardiovasc Med. 2023.