Mucana Pruriens for dyskinesias in Parkinson's disease

描述（由申请人提供）： Aurveda是印度的一种独立的医疗实践。最近的研究表明，Aurvedic药用化合物Mucuna pruriens在改善帕金森症方面是有效的。帕金森病（PD）患者在使用现代医学中使用的现有药物进行3-5年的药物治疗后会出现严重且通常致残的副作用。对Aurvedic经文的回顾和对Aurveda从业者的咨询表明，接受含有Mucuna pruriens的Aurvedic药物治疗的PD患者不会出现致残性副作用。我们建议检查的影响，给药毛豆pruriens 1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）治疗帕金森病的猴子，一个很好的表征PD的动物模型，用于研究运动障碍。在拟议的实验中将使用两个单独的假设。1)用Mucuna pruriens预处理帕金森病猴将预防MPTP处理的猴中药物诱导的运动障碍，并且2）对具有药物诱导的运动障碍的MPTP处理的猴共同施用Mucuna pruriens将改善这些动物中的运动障碍。这些实验将在2年内使用共计8只成年恒河猴，研究者将使用行为成套测试（BBT）定期评估动物。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评估帕金森综合征的严重程度，并将动物随机分为3个相等的组。第1组动物将接受每日剂量的Mucuna pruriens，持续30天，然后用抑制剂高剂量的左旋多巴/苯瑟糖苷的甲酯处理以诱导运动障碍。第2组动物将接受安慰剂30天，然后用高剂量的左旋多巴/苯瑟糖苷的甲酯诱导运动障碍。将由对治疗组设盲的研究者使用BBT评估行为效应。在完成3个月的行为测试后，第I组动物将开始接受安慰剂代替刺毛油麻藤，第2组动物将开始接受刺毛油麻藤。将对所有动物进行额外12个月的行为学试验。将使用脑组织学检查和微阵列分析验证2组动物之间的差异（如果存在）。这些实验将确定Mucuna pruriens是否对PD中发生的药物诱导的运动障碍具有预防或改善作用。我们的提案符合NCCAM的R21应用标准，这将产生关于传统草药对PD并发症的可能有效性的初步数据，并最终开发出治疗药物。

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.