Preventing levodopa induced dyskinesia in Parkinsonâs Disease with Statins

用他汀类药物预防帕金森病中左旋多巴引起的运动障碍

基本信息

  • 批准号:
    10291805
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-04-01 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

The purpose of this project is to determine whether HMG-CoA reductase inhibitors (statins) will inhibit the progression of levodopa (LD) induced dyskinesia in Parkinson disease (PD) given that rodent and primate models have carefully demonstrated this. LD is the most important medication that Veterans with PD will take to control their symptoms and has remained so since its discovery in the 1960s. Unfortunately, early recognition of the benefits of LD against the stiffness, slowness and tremor of PD was accompanied in many cases by the side effect of dyskinesia, or unwanted purposeless excessive movements. Dyskinesias, which appear choreic, jerky or dystonic become more severe over time and have few treatment options, including reducing dopaminergic medications, which can lead to intolerable worsening of parkinsonian symptoms. Other options include amantadine, or deep brain stimulation. These treatments are not suitable for all patients, illustrating the need for other strategies including preventive, or “disease modifying” approaches. In animal models, statins applied comcomitantly with first ever LD ingestion interrupted the dyskinesia priming process as proven by reduction in not only dyskinesia biomarker levels, but significantly lessened future expression of dyskinesia. In this project, we will perform a retrospective cohort study using VA databases to select 40 Veterans with PD who have been prescribed statins prior to or concomitant to being prescribed LD for PD for several years (giving him/her ample time to potentially develop dyskinesia) and compare with a group of who never used statins. We will measure dyskinesia that has developed in these cohorts precisely using not only current standard methods but our unique methods of data gathering which includes a LD infusion and electronic dyskinesia measurements. We will determine if statin exposure was protective, resulting in less severe dyskinesia expression years later. We will also study a third 40 subject cohort prescribed a statin after LD initiation, to see if the eventual severity of dyskinesia is lessened, implying slowing of rate of dyskinesia progression. (secondary prevention). The power of the VA databases is in identifying subjects with the correct order of administration of statin and levodopa as well as continued administration through the years, along with baseline characteristics so that appropriate cohorts can be generated in sufficient numbers. By the end of this project, we will determine if statin exposure at the beginning of LD use is important to retarding the priming process for dyskinesia development, and whether there is still room for modifying the rate of progression of dyskinesia even if started late. If our study shows that statins do modify the rate of dyskinesia progression, then a multicenter prospective trial of statins would certainly be warranted. A means of preventing a dreaded complication of PD treatment would be welcome.
本项目的目的是确定HMG-CoA还原酶抑制剂是否 他汀类药物将抑制帕金森病患者左旋多巴(LD)诱导的运动障碍的进展 鉴于啮齿动物和灵长类动物模型已经仔细证明了这一点, LD是最重要的药物,退伍军人与PD将采取控制他们的 自1960年代发现以来一直如此。不幸的是, 认识到LD对PD的僵硬,缓慢和震颤的益处, 在许多情况下伴随着运动障碍的副作用,或不必要的无症状, 过度运动。运动障碍,这似乎舞蹈,抽搐或肌张力障碍成为 随着时间的推移,病情越来越严重,治疗选择很少,包括减少 多巴胺能药物,这可能导致帕金森病的不可忍受的恶化 症状其他选择包括金刚烷胺或深部脑刺激。这些 治疗并不适合所有患者,说明需要其他策略 包括预防或“疾病改善”方法。在动物模型中, 与首次LD摄入同时应用中断了运动障碍引发 这一过程不仅通过运动障碍生物标志物水平的降低, 减少运动障碍的未来表达。在这个项目中,我们将进行回顾 使用VA数据库进行队列研究,选择40名已接受 在处方LD治疗PD之前或同时处方他汀类药物, 年(给他/她足够的时间来潜在地发展运动障碍),并与 从未使用过他汀类药物的人群。我们将测量运动障碍, 这些队列不仅使用了目前的标准方法, 数据收集方法,包括LD输注和电子运动障碍 测量.我们将确定他汀类药物暴露是否具有保护作用, 几年后表现出严重的运动障碍。我们还将研究第三个40名受试者队列 在LD开始后开了他汀类药物,看看运动障碍的最终严重程度是否 减轻,意味着运动障碍进展的速率减慢。(二级预防)。 VA数据库的力量在于以正确的顺序识别受试者 他汀类药物和左旋多巴的给药以及通过 沿着年,以及基线特征,以便生成适当的队列 足够的数量。在本项目结束时,我们将确定他汀类药物暴露在 开始使用LD对于延迟运动障碍的启动过程是重要的 发展,以及是否仍有修改进展速度的余地, 运动障碍,即使开始晚。如果我们的研究表明他汀类药物确实可以改变 运动障碍进展,那么他汀类药物的多中心前瞻性试验肯定是 有正当理由预防PD治疗可怕并发症的一种方法是 客气

项目成果

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Kathryn Anne Chung其他文献

Kathryn Anne Chung的其他文献

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{{ truncateString('Kathryn Anne Chung', 18)}}的其他基金

Preventing levodopa induced dyskinesia in Parkinsonâs Disease with Statins
用他汀类药物预防帕金森病中左旋多巴引起的运动障碍
  • 批准号:
    9922658
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
Preventing levodopa induced dyskinesia in Parkinsonâs Disease with Statins
用他汀类药物预防帕金森病中左旋多巴引起的运动障碍
  • 批准号:
    10903709
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
Preventing levodopa induced dyskinesia in Parkinsonâs Disease with Statins
用他汀类药物预防帕金森病中左旋多巴引起的运动障碍
  • 批准号:
    10427233
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
Reducing Dyskinesia in Parkinson Disease with Omega-3 Fatty Acids
使用 Omega-3 脂肪酸减少帕金森病的运动障碍
  • 批准号:
    8453246
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Reducing Dyskinesia in Parkinson Disease with Omega-3 Fatty Acids
使用 Omega-3 脂肪酸减少帕金森病的运动障碍
  • 批准号:
    8245338
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
CHOLINERGIC AUGMENTATION MAY REDUCE SYMPTOMS IN IDIOPATHIC CHOREA
增强胆碱能可减轻特发性舞蹈病的症状
  • 批准号:
    7206611
  • 财政年份:
    2005
  • 资助金额:
    --
  • 项目类别:
CHOLINERGIC AUGMENTATION MAY REDUCE TREMOR IN ASSOCIATION WITH DYSTONIA
胆碱能增强可能会减少与肌张力障碍相关的震颤
  • 批准号:
    7206610
  • 财政年份:
    2005
  • 资助金额:
    --
  • 项目类别:

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