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.
