柳叶刀:糖尿病药物或可用于治疗帕金森病
2017/08/05
伦敦大学学院领导的一项新研究发现,通常用于治疗糖尿病的药物艾塞那肽可能具有改善帕金森病的潜力。该研究发表The Lancet期刊上,研究发现,帕金森病患者每周注射艾塞那肽,持续1年后运动能力出现改善。


伦敦大学学院领导的一项新研究发现,通常用于治疗糖尿病的药物艾塞那肽可能具有改善帕金森病的潜力。该研究发表The Lancet期刊上,研究发现,帕金森病患者每周注射艾塞那肽,持续1年后运动能力出现改善。

该研究的资深作者Tom Foltynie教授说:“这是一个非常有希望的发现,因为药物具有影响疾病进程的潜力,而不仅仅改善症状。 “现有的治疗方法只能在几年内缓解部分症状,但疾病仍然会继续恶化。”

持续注射艾塞那肽帕金森病得以改善

研究人员跟踪了60名帕金森病患者,这些患者除使用常规药物之外,每周注射一次艾塞那肽或安慰剂,持续48周。他们发现,使用艾塞那肽的患者在48周后表现出更好的运动功能(治疗结束后继续12周的随访)。注射安慰剂的人在48周和60周的测试中运动评分都出现下降。

参与者在试验期间没有自述发生超过常规药物治疗范围之外的明显改善。他们在暂时停用所有药物时进行测试,以确定疾病本身如何进展。这项研究并没有确定药物是否能够修正疾病本身,所以接下来的研究将更加全面地进行调查。

艾塞那肽或可作用于大脑中的GLP-1受体

帕金森病的发病率约为1/500,是全球第二大常见的神经退行性疾病。在出现明显症状时,大脑中70%的多巴胺能神经元已经受到累及。该病导致肌肉僵硬,运动缓慢,震颤,睡眠障碍,慢性疲劳和生活质量受损。

艾塞那肽是1型胰高血糖素样肽(GLP-1)受体激动剂的合成物,2006年已被FDA批准用于治疗2型糖尿病,目前全球约有6百万糖尿病患者用该药。GLP-1受体也在大脑中被发现,以前的研究表明,激活这些受体可以增强多巴胺连接的功能,发挥抗炎作用,改善能量产生和开启细胞存活信号。此前在动物模型中的证据也表明艾塞那肽可改善运动性能。由Foltynie教授领导的团队的研究进一步证实了艾塞那肽对帕金森病患者的作用。

在临床使用前还需要进一步研究

该研究由The Michael J. Fox Foundation for Parkinson's Research (MJFF)资助,MJFF研究计划高级副总裁Brian Fiske博士说:“使用批准药物治疗另一种疾病,为帕金森病的治疗发展提供了新的途径。这项研究证明有理由继续验证艾塞那肽在帕金森病中的作用。但是在进一步了解该药对帕金森病的安全性和影响之前,临床医生和患者不应当将艾塞那肽添加到他们的治疗方案中。

该研究的第一作者Dilan Athauda 博士说:“虽然我们对研究结果很乐观,但还有更多的实验需要做,在新治疗可以批准和准备使用之前还需要好几年的时间,我们也希望了解为什么艾塞那肽的效果因人而异。”

研究人员计划下一步利用更多的参与者来进行长期研究,调查生活质量是否有明显的改善。

参考资料:

Diabetes drug shows potential as disease-modifying therapy for Parkinson's disease

Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial

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  • Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial

    Summary Background Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. Methods In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. Eligible patients were aged 25–75 years, had idiopathic Parkinson's disease as measured by Queen Square Brain Bank criteria, were on dopaminergic treatment with wearing-off effects, and were at Hoehn and Yahr stage 2·5 or less when on treatment. Randomisation was by web-based randomisation with a two strata block design according to disease severity. Patients and investigators were masked to treatment allocation. The primary outcome was the adjusted difference in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. All efficacy analyses were based on a modified intention-to-treat principle, which included all patients who completed any post-randomisation follow-up assessments. The study is registered at ClinicalTrials.gov (NCT01971242) and is completed. Findings Between June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI −2·6 to 0·7) in the exenatide group and worsened by 2·1 points (−0·6 to 4·8) in the placebo group, an adjusted mean difference of −3·5 points (−6·7 to −0·3; p=0·0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions. Interpretation Exenatide had positive effects on practically defined off-medication motor scores in Parkinson's disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson's disease, and effects on everyday symptoms should be examined in longer-term trials. Funding Michael J Fox Foundation for Parkinson's Research.

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