Mucana Pruriens for dyskinesias in Parkinson's disease

Mucana Pruriens 治疗帕金森病运动障碍

• 批准号: 7216097
• 负责人: THYAGARAJAN SUBRAMANIAN
• 金额: $ 18.31万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 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 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7216097
• 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）： 奥吠陀是印度的宗教医学实践。最近的调查表明，奥吠陀药物粘膜瘤可有效改善帕金森氏症。经过3 - 5年的医疗疗法，帕金森氏病（PD）患者患有严重且经常残疾的副作用，目前在现代医学中使用的药物。审查奥吠陀经文并与奥吠陀的从业者进行咨询表明，用含有粘膜pruriens的超甲室药物治疗的PD患者不会产生残疾的副作用。我们建议检查对1-甲基-4-苯基-1、2、3、6-四氢吡啶（MPTP）处理的帕金森猴的甲基-4-苯基-1、2、3、6-苯基-1、2、3、3、6-苯基-1、2、3、3、6-苯基-1-苯基-1、2、3、6-甲基-1-苯基-1、2、3、6-甲基-1-苯基-1、2、3、6-甲基甲基猴的猴子的影响，这是一种用于研究dyskinesias的PD动物模型。在提出的实验中将使用两个单独的假设。 1）用粘膜pruriens预处理帕金森猴会防止在MPTP处理的猴子中进行药物诱发的运动障碍和2）2）粘膜pruriens促粘膜促粘液治疗MPTP治疗的猴子与药物诱导的猴子与药物诱发的运动障碍将在这些动物中降低这些动物的运动障碍。这些实验将在2年的时间内使用8种成年恒河猴，将使用行为量测试（BBT）定期评估动物。获得基线BBT数据后，所有动物都将接受全身注射MPTP，以引起双侧帕金森氏症。此后，将使用BBT评估帕金森氏症的严重程度，并将动物随机分为3个相等的组。第1组动物将在治疗前30天接受每日剂量的粘膜，并与左伏达帕/benserainaside的间歇性高剂量的高剂量的甲基酯诱导肌动症。第2组动物将接受安慰剂30天，然后再诱导lyvodopa/benseracide的高剂量高剂量的甲基酯。行为效应将使用对治疗组蒙蔽的研究人员使用BBT进行评估。完成行为测试3个月后，I组动物将开始接受安慰剂，代替粘膜和2组动物，将开始接收粘膜瘤。所有动物将在行为上进行另外的12个月。如果两组动物之间有任何差异，则将使用对大脑和微阵列分析的组织学检查。这些实验将确定粘膜瘤是否对PD中发生的药物诱导的运动障碍的预防或改善作用。我们的建议符合R21 NCCAM应用的标准，该标准将生成有关传统草药药物可能有效性的PD并发症的初步数据，并最终开发治疗剂。