ARA290

Presentation by: Wei (Adelyn) Tsai
Reviewed by: Thia Hanania & Greg Hollenbeck
ARA290 is an amino acid peptide derived from the helix B of erythropoietin (EPO), a hormone involved in the production of red blood cells (Brines & Cerami, 2012). ARA290 is neuroprotective and tissue-protective without causing hematopoietic and thrombotic side effects that are usually seen in patients given exogenous EPO (Brines et al., 2008). Mechanistically, ARA290 acts on innate repair receptor system and initiate persistent signaling cascades that lead to protective and reparative effects in cells and tissues (Collino et al., 2015). Clinically, it was proven that ARA290 is useful for treating sarcoidosis and ARA290 has received US Orphan Drug and Fast Track designations for treating neuropathic pain associated with sarcoidosis (Dahan et al., 2013). Albeit more studies needed, ARA290 may also be efficient for treating other neuroinflammatory diseases (Chen et al., 2014; Liu et al., 2014, Robertson et al., 2013) and may be able to modulate cognitive functions (Cerit et al., 2015; Seeger et al., 2011).
Further studies:
1. Clinical studies on other neuroinflammatory diseases besides sarcoidosis
2. Assess the psychiatric effects of ARA290
3. Develop an oral form of ARA290
References:
Brines, Michael, & Cerami, A. (2012). The receptor that tames the innate immune response. In Molecular medicine (Cambridge, Mass.) (Vol. 18, Issue 1, pp. 486-496). The Feinstein Institute for Medical Research.
doi.org/10.2119/molmed.2011.0...
Brines, Michael, Patel, N. S. A., Villa, P., Brines, C., Mennini, T., De Paola, M.,
Erbayraktar, Z., Erbayraktar, S., Sepodes, B., Thiemermann, C., Ghezzi, P., Yamin, M., Hand, C. C., Xie, Q. W., Coleman, T., & Cerami, A. (2008). Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proceedings of the National Academy of Sciences of the United States of America, 105(31), 10925-10930. doi.org/10.1073/pnas.0805594105
Collino, M., Thiemermann, C., Cerami, A., & Brines, M. (2015). Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin. Pharmacology and Therapeutics, 151, 32-40. doi.org/10.1016/j.pharmthera....
Dahan, A., Dunne, A., Swartjes, M., Proto, P. L., Heij, L., Vogels, O., van Velzen, M., Sarton, E., Niesters, M., Tannemaat, M. R., Cerami, A., & Brines, M. (2013). ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Molecular Medicine, 19(1), 334-345. doi.org/10.2119/molmed.2013.0...
Chen, H., Luo, B., Yang, X., Xiong, J., Liu, Z., Jiang, M., Shi, R., Yan, C., Wu, Y., & Zhang, Z. (2014). Therapeutic effects of nonerythropoietic erythropoietin analog ARA290 in experimental autoimmune encephalomyelitis rat. Journal of Neuroimmunology, 268(1-2), 64-70. doi.org/10.1016/j.jneuroim.20...
Liu, Y., Luo, B., Han, F., Li, X., Xiong, J., Jiang, M., Yang, X., Wu, Y., & Zhang, Z. (2014). Erythropoietin-Derived Nonerythropoietic Peptide Ameliorates Experimental Autoimmune Neuritis by Inflammation Suppression and Tissue Protection. PLoS ONE, 9(3), e90942. doi.org/10.1371/journal.pone....
Robertson, C. S., Garcia, R., Gaddam, S. S. K., Grill, R. J., Cerami Hand, C., Tian, T. S., & Hannay, H. J. (2013). Treatment of Mild Traumatic Brain Injury with an Erythropoietin-Mimetic Peptide. Journal of Neurotrauma, 30(9), 765-774. doi.org/10.1089/neu.2012.2431
Cerit, H., Veer, I. M., Dahan, A., Niesters, M., Harmer, C. J., Miskowiak, K. W.,
Rombouts, S. A. R. B., & Van der Does, W. (2015). Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action. European Neuropsychopharmacology, 25(12), 2289-2299. doi.org/10.1016/j.euroneuro.2...
Seeger, N., Zellinger, C., Rode, A., Roloff, F., Bicker, G., Russmann, V., Fischborn, S., Wendt, H., & Potschka, H. (2011). The erythropoietin-derived peptide mimetic pHBSP affects cellular and cognitive consequences in a rat post-status epilepticus model. Epilepsia, 52(12), 2333-2343. doi.org/10.1111/j.1528-1167.2...