Mucana Pruriens for dyskinesias in Parkinson's disease

描述(由申请人提供)： 奥吠陀是印度坚定不移的医学实践。最近的研究表明，金吠陀药用化合物羊肚菌在改善帕金森病方面是有效的。帕金森氏病(PD)患者在用现代医学中现有的药物进行3-5年的药物治疗后，会出现严重的副作用，通常是致残的。对《奥吠陀》经文的回顾和与《奥吠陀》从业者的咨询表明，接受含有瘙痒粘液的奥吠陀药物治疗的帕金森病患者不会出现致残性副作用。我们建议检查给1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)治疗的帕金森病猴子的治疗效果。帕金森病是一种用于研究运动障碍的帕金森病动物模型。在拟议的实验中，将使用两个不同的假设。1)用瘙痒粘液对帕金森病猴进行预处理，可预防MPTP治疗猴的药源性运动障碍；2)联合MPTP治疗的药物诱发的运动障碍猴，给予瘙痒粘液可改善这些动物的运动障碍。总共8只成年恒河猴将在两年的时间里用于这些实验，研究人员将使用行为组合测试(BBT)对动物进行定期评估。在获得基线BBT数据后，所有动物都将接受MPTP全身注射，以引起稳定的双侧帕金森综合征。此后，将使用BBT评估帕金森综合症的严重程度，并将动物随机分为3组。第1组动物在给予间歇性大剂量左旋多巴甲酯/苯丝氨酸甲酯治疗以诱发运动障碍之前，每天给予30天的瘙痒毛霉菌。第2组动物在诱发运动障碍前30天内给予安慰剂，间歇性高剂量左旋多巴甲酯/苯丝氨酸甲酯。行为效应将由对治疗组盲目的调查人员使用BBT进行评估。在完成3个月的行为测试后，I组动物将开始接受安慰剂替代羊毛膜，第2组动物将开始接受羊毛膜。所有动物都将再接受12个月的行为测试。大脑的组织学检查和微阵列分析将被用来验证两组动物之间的差异。这些实验将确定瘙痒粘菌对帕金森病中发生的药物诱导的运动障碍是否具有预防或改善作用。我们的建议符合NCCAM的R21应用标准，该标准将产生关于传统草药治疗PD并发症的可能有效性的初步数据，并最终开发出一种治疗剂。

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.