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

Michael Brines, Ann N. Dunne, Monique van Velzen, Paolo L. Proto, Claes Goran Ostenson, Rita I. Kirk, Ioannis N. Petropoulos, Saad Javed, Rayaz Malik, Anthony Cerami, Albert Dahan

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Abstract

Although erythropoietin ameliorates experimental type 2 diabetes with neuropathy, serious side effects limit its potential clinical use. ARA 290, a nonhematopoietic peptide designed from the structure of erythropoietin, interacts selectively with the innate repair receptor that mediates tissue protection. ARA 290 has shown efficacy in preclinical and clinical studies of metabolic control and neuropathy. To evaluate the potential activity of ARA 290 in type 2 diabetes and painful neuropathy, subjects were enrolled in this phase 2 study. ARA 290 (4 mg) or placebo were self-administered subcutaneously daily for 28 d and the subjects followed for an additional month without further treatment. No potential safety issues were identified. Subjects receiving ARA 290 exhibited an improvement in hemoglobin A(1c) (Hb A(1c)) and lipid profiles throughout the 56 d observation period. Neuropathic symptoms as assessed by the PainDetect questionnaire improved significantly in the ARA 290 group. Mean corneal nerve fiber density (CNFD) was reduced significantly compared with normal controls and subjects with a mean CNFD >1 standard deviation from normal showed a significant increase in CNFD compared with no change in the placebo group. These observations suggest that ARA 290 may benefit both metabolic control and neuropathy in subjects with type 2 diabetes and deserves continued clinical evaluation.

Original languageEnglish
Pages (from-to)658-666
Number of pages9
JournalMolecular medicine (Cambridge, Mass.)
Volume20
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Brines, M., Dunne, A. N., van Velzen, M., Proto, P. L., Ostenson, C. G., Kirk, R. I., Petropoulos, I. N., Javed, S., Malik, R., Cerami, A., & Dahan, A. (2014). ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Molecular medicine (Cambridge, Mass.), 20, 658-666. https://doi.org/10.2119/molmed.2014.00215