Mucana Pruriens for dyskinesias in Parkinson's disease

Mucana Pruriens 治疗帕金森病运动障碍

• 批准号: 6870829
• 负责人: THYAGARAJAN SUBRAMANIAN
• 金额: $ 19.13万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6870829
• 关键词: Macaca mulatta; Parkinson' s disease; abnormal involuntary movement; alternative medicine; antiparkinson drugs; behavior test; chemoprevention; combination chemotherapy; disease /disorder model; disease /disorder prevention /control; drug adverse effect; drug screening /evaluation; folk medicine; histology; human therapy evaluation; levodopa; longitudinal animal study; medical complication; medicinal plants; microarray technology; nervous system disorder chemotherapy; nonhuman therapy evaluation; plant extracts

DESCRIPTION (provided by applicant): Aurveda is an indegenious medical practice of India. Recent investigations indicate the Aurvedic medicinal compound Mucuna pruriens is effective in improving Parkinsonism. Patients with Parkinson's disease (PD) develop severe and often disabling side effects after 3-5 years of medical therapy with currently available medications used in modern medicine. Review of Aurvedic scriptures and consultation with practitioners of Aurveda indicate that PD patients treated with Aurvedic medications containing Mucuna pruriens do not develop disabling side effects. We propose to examine the effects of administering Mucuna pruriens to 1- methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated parkinsonian monkeys, a well characterized animal model of PD used to study dyskinesias. Two separate hypotheses will be utilized in the proposed experiments. 1) Pretreatment of parkinsonian monkeys with Mucuna pruriens will prevent drug induced dyskinesias in MPTP treated monkeys and 2) coadministrarion of Mucuna pruriens to MPTP treated monkeys with drug induced dyskinesias will ameliorate dyskinesia in these animals. A total of 8 Adult Rhesus monkeys will be used in these experiments over a period of 2 years, Animals will be periodically assessed by investigators using a behavioral battery of tests (BBT). After obtaining baseline BBT data, all animals will receive systemic injections of MPTP to cause stable bilateral Parkinsonism. Thereafter the severity of Parkinsonism will be assessed using BBT and the animals will be randomized into 3 equal groups. Group 1 Animals will receive daily dose of Mucuna pruriens for 30 days prior to treatment with intermittant high doses of methyl ester of levodopa/benseraside to induce dyskinesias. Group 2 animals will receive placebo for 30 days prior to induction of dyskinesias with intermittant high doses of methyl ester of levodopa/benseraside. Behavioral effects will be assessed using BBT by investigators blinded to the treatment groups. After completion of behavioral testing for 3 months, Group I animals will begin to receive placebo in place of Mucuna pruriens and Group 2 animals will start recieving Mucuna pruriens. All animals will be behaviorally tested for an additional 12 months. Histological examination of the brain and microarray analysis will be used verify differences if any between the 2 groups of animals. These experiments will determine if Mucuna pruriens has preventative or ameliorative effects on drug induced dyskinesias that occur in PD. Our proposal meets the criteria of R21 application of NCCAM that will generate preliminary data on possible effectiveness of a traditional herbal drug for complications of PD with eventual development of a therapeutic agent.

描述（由申请人提供）： Aurveda 是印度本土的医疗实践。最近的研究表明，奥吠陀药用化合物黧豆可有效改善帕金森症。帕金森病 (PD) 患者在使用现代医学现有药物治疗 3-5 年后会出现严重且常常致残的副作用。对 Aurvedic 经典的回顾以及与 Aurveda 从业者的咨询表明，使用含有黧豆的 Aurvedic 药物治疗的 PD 患者不会出现致残的副作用。我们建议检查对 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 治疗的帕金森猴施用黧豆的效果，帕金森猴是一种用于研究运动障碍的特征明确的帕金森病动物模型。在提议的实验中将使用两个独立的假设。 1) 用黧豆预处理帕金森病猴将预防 MPTP 治疗的猴子中药物引起的运动障碍，2) 对患有药物引起的运动障碍的 MPTP 治疗的猴子共同施用黧豆将改善这些动物的运动障碍。这些实验将在 2 年内使用总共 8 只成年恒河猴，研究人员将使用一系列行为测试 (BBT) 定期对动物进行评估。获得基线BBT数据后，所有动物将接受MPTP全身注射以引起稳定的双侧帕金森病。此后，将使用 BBT 评估帕金森症的严重程度，并将动物随机分为 3 个相等的组。第1组动物将每天接受黧豆剂量30天，然后用间歇性高剂量左旋多巴/苯塞拉苷甲酯治疗以诱导运动障碍。第2组动物将接受安慰剂30天，然后间歇性高剂量左旋多巴/苯塞拉苷甲酯诱导运动障碍。行为影响将由对治疗组不知情的研究人员使用 BBT 进行评估。完成 3 个月的行为测试后，第 1 组动物将开始接受安慰剂代替黧豆，第 2 组动物将开始接受黧豆。所有动物都将接受额外 12 个月的行为测试。将使用大脑的组织学检查和微阵列分析来验证两组动物之间是否存在差异。这些实验将确定黧豆是否对帕金森病中药物引起的运动障碍具有预防或改善作用。我们的提案符合 NCCAM R21 应用的标准，该标准将生成关于传统草药对 PD 并发症的可能有效性的初步数据，并最终开发出治疗剂。