Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom.
J Clin Invest. 2013 Jun;123(6):2730-6. doi: 10.1172/JCI68295.
BACKGROUND. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. METHODS. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson's disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). RESULTS. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). CONCLUSION. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD.
Clinicaltrials.gov NCT01174810.
Cure Parkinson's Trust.
背景。人们对更快速、更具成本效益的方法越来越感兴趣，这些方法可用于研究已批准用于治疗另一种疾病的药物。Exenatide 是一种 2 型糖尿病治疗药物，已在神经退行性变的临床前模型中显示出具有神经保护/神经修复特性。方法。作为概念验证，我们使用单盲试验设计，评估了 45 名患有中度帕金森病（PD）的患者的进展情况，这些患者随机分配接受皮下注射 Exenatide 治疗 12 个月或作为对照组。在停用常规 PD 药物过夜后，使用盲法视频评估运动障碍协会统一帕金森病评定量表（MDS-UPDRS）以及几项非运动测试，对他们的 PD 进行比较，基线时、6 个月时、12 个月时以及进一步的 2 个月洗脱期（14 个月时）。结果。Exenatide 耐受性良好，尽管常见体重减轻，且单例患者出现 l-dopa 剂量失败。与对照组相比，Exenatide 组的单盲评分提示 PD 在运动和认知测量方面具有临床相关的改善。与对照组相比，Exenatide 治疗患者在 12 个月时 MDS-UPDRS 的平均改善为 2.7 分，而对照组的平均下降为 2.2 分（P = 0.037）。结论。这些结果表明，在进行潜在疾病修饰药物在 PD 中进行双盲试验所需的重大投资之前，可以通过一种潜在的具有成本效益的方法获得可能的生物学效应的初步临床数据。试验注册：Clinicaltrials.gov NCT01174810。资金来源：治愈帕金森氏症信托基金。
