ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.
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.
Araim Pharmaceuticals, Tarrytown, New York, United States of America.
Michael
M
Brines
Araim Pharmaceuticals, Tarrytown, New York, United States of America.
Ann N
AN
Dunne
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Monique
M
van Velzen
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Paolo L
PL
Proto
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Claes-Goran
CG
Ostenson
Araim Pharmaceuticals, Tarrytown, New York, United States of America.
Rita I
RI
Kirk
Centre for Diabetes and Endocrinology, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, United Kingdom.|Weill Cornell Medical College in Qatar, Qatar Foundation, Doha, Qatar.
Ioannis N
IN
Petropoulos
Centre for Diabetes and Endocrinology, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Saad
S
Javed
Centre for Diabetes and Endocrinology, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, United Kingdom.|Weill Cornell Medical College in Qatar, Qatar Foundation, Doha, Qatar.
Rayaz A
RA
Malik
Araim Pharmaceuticals, Tarrytown, New York, United States of America.
Anthony
A
Cerami
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Albert
A
Dahan
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004921:Erythropoietin / Q000031:analogs & derivatives; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D004921:Erythropoietin; D006442:Glycated Hemoglobin; D008055:Lipids; D009842:Oligopeptides; C517652:hemoglobin A1c protein, human; C576178:cibinetide