Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study.

OBJECTIVE: To investigate whether Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in all tropical areas worldwide, may be used as alternative source of levodopa for indigent individuals with Parkinson disease (PD) who cannot afford long-term therapy with marketed levodopa preparations. METHODS: We investigated efficacy and safety of single-dose intake of MP powder from roasted seeds obtained without any pharmacologic processing. Eighteen patients with advanced PD received the following treatments, whose sequence was randomized: (1) dispersible levodopa at 3.5 mg/kg combined with the dopa-decarboxylase inhibitor benserazide (LD+DDCI; the reference treatment); (2) high-dose MP (MP-Hd; 17.5 mg/kg); (3) low-dose MP (MP-Ld; 12.5 mg/kg); (4) pharmaceutical preparation of LD without DDCI (LD-DDCI; 17.5 mg/kg); (5) MP plus benserazide (MP+DDCI; 3.5 mg/kg); (6) placebo. Efficacy outcomes were the change in motor response at 90 and 180 minutes and the duration of on state. Safety measures included any adverse event (AE), changes in blood pressure and heart rate, and the severity of dyskinesias. RESULTS: When compared to LD+DDCI, MP-Ld showed similar motor response with fewer dyskinesias and AEs, while MP-Hd induced greater motor improvement at 90 and 180 minutes, longer ON duration, and fewer dyskinesias. MP-Hd induced less AEs than LD+DDCI and LD-DDCI. No differences in cardiovascular response were recorded. CONCLUSION: Single-dose MP intake met all noninferiority efficacy and safety outcome measures in comparison to dispersible levodopa/benserazide. Clinical effects of high-dose MP were similar to levodopa alone at the same dose, with a more favorable tolerability profile. CLINICALTRIALSGOV IDENTIFIER: NCT02680977.

The effect of levodopa benserazide hydrochloride on homocysteinemia levels in patients with Parkinson's disease and treatment of hyperhomocysteinemia.

OBJECTIVE: This study aims to investigate hyperhomocysteinemia (HHcy) resulted from treatment in patients with Parkinson's disease (PD) and to evaluate the therapeutic outcome of HHcy. PATIENTS AND METHODS: Ninety-three newly diagnosed PD patients were divided into Madopar group (treated with Madopar) and non-Madopar group (not treated with Madopar). Plasma Hcy levels were measured. Five months later, 67 patients presenting with HHcy were randomly divided into treatment group (n = 34) (receiving methylcobalamin 500 µg, tid, and folic acid 50 mg, tid, orally) and control group (n = 33).  Madopar dosage was maintained in both groups. MRI examination was performed to detect cerebral ischemia and patients were evaluated by Webster's rating scale. Plasma Hcy levels were measured at 3-month follow-up. Webster's scores and MRI were performed at 6-month follow-up. RESULTS: At the initial visit, Hcy levels of patients of Madopar group were significantly higher than those of non-Madopar group (18.52 ± 6.48 µmol/L) vs. (15.78 ± 3.42), p < 0.05]. At 5-month follow-up, patients of the non-Madopar group presented significantly increased Hcy levels (18.97 ± 7.42 µmol/L) compare with pre-treatment Hcy levels (p < 0.05), whereas Hcy levels were slightly increased in patients of Madopar group (20.61 ± 7.87 µmol/L, p > 0.05). In the treatment group, serum Hcy levels were significantly decreased after 3-month treatment with methylcobalamin and folic acid (p < 0.01). However, serum Hcy levels were not significantly changed in patients of the control group. In addition, in the treatment group, no patient presented ischemic stroke with clinical symptoms and four patients were confirmed with new cerebral ischemic and lacunar lesions by MRI examination. However, in the control group, two ischemic strokes with clinical symptoms and 11 new cerebral ischemic and lacunar lesions were detected. Significant differences were observed between two groups (p < 0.05). Furthermore, post-treatment modified Webster scores were significantly decreased than pre-treatment scores for both groups. However, no significant differences were found between groups (p > 0.05). CONCLUSIONS: Oral administration of Levodopa in the treatment of PD can cause HHcy, which can result in increased occurrence of ischemic stroke. Supplementation of methylcobalamin and folic acid can effectively reduce Hcy level and thereby prevent the occurrence of ischemic stroke.

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (ß) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

[Effects of "attenuation and synergia" for Bushenhuoxue Granules on Parkinson's patients].

OBJECTIVE: To study the effects of "Attenuation and Synergia" for Bushenhuoxue Granules (BSHXG) on Parkinson's patients. METHODS: 120 patients were enrolled and divided into two groups randomly, the control group were treated with placebo and treatment group with BSHXG, both groups based on Madopar treatment. Double-blinded clinical trial was adopted in treatment period. Follow-up period for 6 months. Usage of Madopar and score of treatment complications were adopted to measure related motor complications before and after treatment. RESULTS: Usage of Madopar and score of treatment complications in treatment group were decreased (P < 0.05). No adverse effects were found in this trial. CONCLUSION: BSHXG can decrease the side-effects of Madopar and put off the development of PD. The effects of "Attenuation and Synergia" of BSHXG becomes clear with time.

[Effects of bushenhuoxue granules on sleep quality in Parkinson's patients].

OBJECTIVE: To study the effects of Bushenhuoxue Granules on Parkinson's disease sleep scale (PDSS) score in Parkinson's patients. METHODS: 120 patients were enrolled and divided into two groups randomly,the control group were treated with placebo and treatment group with Bushenhuoxue Granules, both group based on Madopar treatment. Double-blinded clinical trial was adopted in treatment period. Follow-up period for 6 months, PDSS was adopted to measure sleep condition of PD patients at baseline time, after 3 months and after 9 months. RESULTS: Bushenhuoxue Granules treatment group showed a higher efficacy than the placebo group in relieving the sleep disorders of Parkinson disease patients,both in treatment and follow-up period (P < 0.01). No adverse effects were found in this trial. CONCLUSIONS: Bushenhuoxue Granules can markedly improve sleep disorders in Parkinson's patients. The effects are stable and obvious along with the process of treatment.

[Effect of TCM treatment according to syndrome differentiation in enhancing curative effect and reducing side-effect of madopa].

OBJECTIVE: To observe the effect of TCM treatment according to syndrome differentiation in en-hancing curative effect and reducing side-effect of madopa in patients with Parkinson' s disease (PD). METHODS: The trial was conducted in 101 PD patients with a prospective stratified randomized and controlled method. They were assigned to group 1 in which the patients of rigidity were treated with Pabing Recipe 1 (PR1) plus Madopa tablets, group 2 with those of tremor given Pabing Recipe 3 (PR3) plus Madopa tablets, and group 3 given a fixed Chinese recipe plus Madopa tablets as the control. The treatment course for all the groups was 3 months. Clinical efficacy was evaluated with unified Parkinson's disease rating scale (UPDRS) and the adverse reactions observed before and after treatment. RESULTS: After treatment, the 4 partial scores and the total score of UPDRS decreased significantly in group 2 (P<0.01), and the former of them and the total score declined in group 1 and 3 (P<0.01), the improvement was better in group 1 and 2 than that in group 3 (P<0.01); the improvement rate in group 1 to 3 was 95.5%, 100.0% and 83.7%, respectively, which was significantly higher in group 1 and 2 than that in group 3 (P<0.05). CONCLUSION: TCM treatment according to syndrome differentiation could improve the clinical symptoms and reduce complications in PD patients, which could enhance curative effect and reduce side-effect of madopa.

Complicaciones motoras precoces en parkisonianos de novo tratados con L-Dopa más inhibidor periférico de la decarboxilasa / Early motor complications in parkisonians of novo treated with L-Dopa plus descarboxylase inhibitor

En una serie de 27 pacientes con enfermedad de Parkinson esencial de novo, en grado 2,7 de Hoehn y Yahr como promedio, con un rango de 1 a 4, tratados con levodopa más benserazida durante 16 semanas, se observaron efectos motores adversos leves a moderados en 12 casos (44,4 por ciento): 8 pacientes presentaron diskinesias, 7 distonías y un deterioro de final de dosis. La dosis máxima de levodopa ID utilizada fue de 750 mg los que alcanzaron a la tercera semana, previo ascenso paulatino desde 125 mg inicial. Posteriormente, se buscó la mínima dosis efectiva la cual correspondió a una cifra de 475 mg como media con un rango de 250 a 750 mg correspondiente a 49,7 por ciento de reducción, lográndose un efecto antiparkinsoniano similar al obtenido con la dosis máxima. Se discuten los posibles factores que hayan influido en el porcentaje alto de efectos motores adversos encontrados en esta serie

[The effect of withdrawal from L-DOPA compounds on pathochemical changes of motor structures of the brain caused by them]. / Vliianie otmeny preparatov L-DOFA na vyzvannye imi patokhimicheskie izmeneniia dvigatel'nykh struktur mozga.

Activities of enzymes of protein metabolism (aminopeptidase, acid phosphatase), of neurotransmitters (monoamine oxidase, acetylcholinesterase) and oxidative metabolism (glutamate- and glucose-6-phosphate dehydrogenases) were studied by quantitative cytochemical procedures in brain motor structures (sensomotor cortex, caudate nucleus) as well as in brain tissues not related directly to locomotory functions (n. accumbens, hippocampus) of rats exhibiting high and low locomotory activities after repeated L-DOPA administration within 14 days as well as within 14 days after drug discontinuation. That of L-dopa (madopare) caused alterations in the enzymatic activity in the brain motor structures of rats, mainly, with a high locomotory activity. It may be suggested that madopare withdrawal-induced decreases in MAO activity might be, to a certain extent, a cause of dyskinesias occurring after discontinuation of L-DOPA drugs.