ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes
ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes
复制标题
DOI：
10.2119/molmed.2014.00215
复制
发表时间：
2014-07-01
影响因子：
5.7
通讯作者：
Dahan, Albert
中科院分区：
文献类型：
--
作者：
Brines, Michael;Dunne, Ann N.;Dahan, Albert
虽然促红细胞生成素可以改善伴有神经病变的实验性2型糖尿病，但严重的副作用限制了其潜在的临床应用。ARA 290是一种由促红细胞生成素结构设计的非造血肽，可选择性地与介导组织保护的先天修复受体相互作用。ARA 290在代谢控制和神经病变的临床前和临床研究中显示出疗效。为了评估ARA 290在2型糖尿病和疼痛性神经病变中的潜在活性，受试者参加了这项2期研究。ARA 290 （4mg）或安慰剂每日皮下自我给药28天，受试者在没有进一步治疗的情况下再随访一个月。没有发现潜在的安全问题。在整个56天的观察期内，接受ARA 290治疗的受试者表现出血红蛋白A(1c) （Hb A(1c)）和脂质谱的改善。通过PainDetect问卷评估的神经性症状在ARA 290组中显著改善。与正常对照相比，平均角膜神经纤维密度（CNFD）显著降低，与正常对照相比，平均角膜神经纤维密度（CNFD）偏离正常值bb0.1标准差的受试者的CNFD显著增加，而安慰剂组无变化。这些观察结果表明，ARA 290可能有益于2型糖尿病患者的代谢控制和神经病变，值得继续进行临床评估。
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.