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Parkinson drugs trials

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https://www.readbyqxmd.com/read/28409730/chronic-multisite-brain-recordings-from-a-totally-implantable-bidirectional-neural-interface-experience-in-5-patients-with-parkinson-s-disease
#1
Nicole C Swann, Coralie de Hemptinne, Svjetlana Miocinovic, Salman Qasim, Jill L Ostrem, Nicholas B Galifianakis, Marta San Luciano, Sarah S Wang, Nathan Ziman, Robin Taylor, Philip A Starr
OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network...
April 14, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28387682/exendin-4-treatment-improves-lps-induced-depressive-like-behavior-without-affecting-pro-inflammatory-cytokines
#2
Filip Ventorp, Cecilie Bay-Richter, Analise Sauro Nagendra, Shorena Janelidze, Viktor Sjödahl Matsson, Jack Lipton, Ulrika Nordström, Åsa Westrin, Patrik Brundin, Lena Brundin
BACKGROUND: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration...
April 4, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28386306/a-preclinical-systematic-review-of-ginsenoside-rg1-in-experimental-parkinson-s-disease
#3
REVIEW
Liang Song, Meng-Bei Xu, Xiao-Li Zhou, Dao-Pei Zhang, Shu-Ling Zhang, Guo-Qing Zheng
To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson's disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P < 0...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28385039/evidence-based-review-of-pharmacotherapy-used-for-parkinson-s-disease-psychosis
#4
Kyle John Wilby, Eric G Johnson, Hannah E Johnson, Mary H H Ensom
OBJECTIVE: To summarize and evaluate the existing literature regarding medications to treat Parkinson's disease (PD) psychosis. DATA SOURCES: MEDLINE (1946 to March 2017), EMBASE (1980 to March 2017), CINAHL (1982 to March 2017), and PsychInfo (1887 to March 2017) were searched using the following terms: Parkinson disease, Parkinson's disease, psychotic disorders, psychosis, delusions, and hallucinations. STUDY SELECTION AND DATA EXTRACTION: The search was limited to randomized controlled trials (RCTs) reporting human outcomes...
April 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28370447/trial-of-dextromethorphan-quinidine-to-treat-levodopa-induced-dyskinesia-in-parkinson-s-disease
#5
Susan H Fox, Leonard Verhagen Metman, John G Nutt, Matthew Brodsky, Stewart A Factor, Anthony E Lang, Laura E Pope, Nadine Knowles, João Siffert
BACKGROUND: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia. METHODS: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout...
March 30, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28360997/imaging-biomarkers-in-parkinson-s-disease-and-parkinsonian-syndromes-current-and-emerging-concepts
#6
REVIEW
Usman Saeed, Jordana Compagnone, Richard I Aviv, Antonio P Strafella, Sandra E Black, Anthony E Lang, Mario Masellis
Two centuries ago in 1817, James Parkinson provided the first medical description of Parkinson's disease, later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants (also termed, Parkinson-plus syndromes). Today, Parkinson's disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 million. Conversely, atypical parkinsonian syndromes encompass a group of relatively heterogeneous disorders that may share some clinical features with Parkinson's disease, but are uncommon distinct clinicopathological diseases...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28359849/a-review-on-traditional-uses-phytochemistry-pharmacology-pharmacokinetics-and-toxicology-of-the-genus-peganum
#7
REVIEW
Shuping Li, Xuemei Cheng, Changhong Wang
ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Peganum have a long history as a Chinese traditional medicine for the treatment of cough, hypertension, diabetes, asthma, jaundice, colic, lumbago, and many other human ailments. Additionally, the plants can be used as an amulet against evil-eye, dye and so on, which have become increasingly popular in Asia, Iran, Northwest India, and North Africa. AIM OF THE REVIEW: The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interaction of the genus Peganum in order to assess the ethnopharmacological use and to explore therapeutic potentials and future opportunities for research...
May 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28349512/chlorpromazine-versus-metiapine-for-schizophrenia
#8
REVIEW
Morteza Zare, Azam Bazrafshan
BACKGROUND: Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine derivative, has been reported to have potent antipsychotic characteristics. However, no evidence currently exists on the effectiveness of chlorpromazine in treatment of people with schizophrenia compared to metiapine, a newer antipsychotic. OBJECTIVES: To compare the effect of chlorpromazine versus metiapine for the treatment of people with schizophrenia SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials in November 2015 and 2016...
March 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28341222/the-science-and-ethics-of-cell-based-therapies-for-parkinson-s-disease
#9
REVIEW
C R Towns
Parkinson's Disease (PD) is an age-related, disabling neurodegenerative disorder. Although sufferers usually respond to dopamine agonists for extended periods, the disease remains progressive and adverse drug effects can compromise effective long term treatment. Cell-based therapies have been the subject of much hype and optimism with regard to PD. Proof of principle was provided in the 1980s with fetal tissue transplantation trials demonstrating successful graft survival. Embryonic stem cells and reprogrammed or transdifferentiated somatic cells may provide alternative sources of tissue with the potential to overcome the material shortages and technical difficulties that have hindered fetal neural transplants...
January 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28303913/multiple-system-atrophy-insights-into-a-rare-and-debilitating-movement-disorder
#10
REVIEW
Florian Krismer, Gregor K Wenning
Multiple system atrophy (MSA) is a devastating and fatal neurodegenerative disorder. The clinical presentation of this disease is highly variable, with parkinsonism, cerebellar ataxia and autonomic failure being the most common - and often debilitating - symptoms. These symptoms progress rapidly, and patients die from MSA-related complications after 9 years of symptom duration on average. Unfortunately, the course of the disease cannot be improved by drug or surgical treatment. In addition, symptomatic treatment options are currently limited, and therapeutic benefits are often only transient...
March 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28299724/convection-enhanced-delivery
#11
REVIEW
A M Mehta, A M Sonabend, J N Bruce
Convection-enhanced delivery (CED) is a promising technique that generates a pressure gradient at the tip of an infusion catheter to deliver therapeutics directly through the interstitial spaces of the central nervous system. It addresses and offers solutions to many limitations of conventional techniques, allowing for delivery past the blood-brain barrier in a targeted and safe manner that can achieve therapeutic drug concentrations. CED is a broadly applicable technique that can be used to deliver a variety of therapeutic compounds for a diversity of diseases, including malignant gliomas, Parkinson's disease, and Alzheimer's disease...
March 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28288201/optokinetic-nystagmus-reflects-perceptual-directions-in-the-onset-binocular-rivalry-in-parkinson-s-disease
#12
Mana Fujiwara, Catherine Ding, Lisandro Kaunitz, Julie C Stout, Dominic Thyagarajan, Naotsugu Tsuchiya
Optokinetic nystagmus (OKN), the reflexive eye movements evoked by a moving field, has recently gained interest among researchers as a useful tool to assess conscious perception. When conscious perception and stimulus are dissociated, such as in binocular rivalry-when dissimilar images are simultaneously presented to each eye and perception alternates between the two images over time-OKN correlates with perception rather than with the physical direction of the moving field. While this relationship is well established in healthy subjects, it is yet unclear whether it also generalizes to clinical populations, for example, patients with Parkinson's disease...
2017: PloS One
https://www.readbyqxmd.com/read/28265459/indirect-tolerability-comparison-of-deutetrabenazine-and-tetrabenazine-for-huntington-disease
#13
Daniel O Claassen, Benjamin Carroll, Lisa M De Boer, Eric Wu, Rajeev Ayyagari, Sanjay Gandhi, David Stamler
BACKGROUND: Vesicular monoamine transporter 2 (VMAT2) inhibitors can improve hyperkinetic movements, and are effective treatment options for chorea of Huntington disease (HD). Tetrabenazine was assessed for treating chorea in the TETRA-HD trial, and while efficacious, there are tolerability concerns possibly due to its pharmacokinetic properties. Deutetrabenazine is a novel VMAT2 inhibitor that contains deuterium, which extends active metabolite half-lives and minimizes drug concentration fluctuations...
2017: Journal of Clinical Movement Disorders
https://www.readbyqxmd.com/read/28246967/the-cognitive-role-of-the-globus-pallidus-interna-insights-from-disease-states
#14
M J Gillies, J A Hyam, A R Weiss, C A Antoniades, R Bogacz, J J Fitzgerald, T Z Aziz, M A Whittington, Alexander L Green
The motor symptoms of both Parkinson's disease and focal dystonia arise from dysfunction of the basal ganglia, and are improved by pallidotomy or deep brain stimulation of the Globus Pallidus interna (GPi). However, Parkinson's disease is associated with a greater degree of basal ganglia-dependent learning impairment than dystonia. We attempt to understand this observation in terms of a comparison of the electrophysiology of the output of the basal ganglia between the two conditions. We use the natural experiment offered by Deep Brain Stimulation to compare GPi local field potential responses in subjects with Parkinson's disease compared to subjects with dystonia performing a forced-choice decision-making task with sensory feedback...
May 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#15
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28202824/-disease-modifying-therapy-for-parkinson-s-disease
#16
Hideki Shimura, Nobutaka Hattori
Currently, treatment of Parkinson's disease aims at alleviating its symptoms. However development of disease-modifying drugs has been a remarkable advancement in recent years. Furthermore, clinical trials of immunotherapy against α-synuclein, a protein involved in the pathogenesis of and lesion expansion in Parkinson's disease, have been initiated. Here, the disease-modifying treatment for patients with Parkinson's disease including the current α-synuclein immunotherapy, gene therapy, protein injection therapy, and cell transplantation therapy, has been reviewed...
February 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28180961/dermal-phospho-alpha-synuclein-deposits-confirm-rem-sleep-behaviour-disorder-as-prodromal-parkinson-s-disease
#17
Kathrin Doppler, Hanna-Maria Jentschke, Lena Schulmeyer, David Vadasz, Annette Janzen, Markus Luster, Helmut Höffken, Geert Mayer, Joachim Brumberg, Jan Booij, Thomas Musacchio, Stephan Klebe, Elisabeth Sittig-Wiegand, Jens Volkmann, Claudia Sommer, Wolfgang H Oertel
Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls...
April 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28157097/combination-therapy-with-zonisamide-and-antiparkinson-drugs-for-parkinson-s-disease-a-meta-analysis
#18
Shinji Matsunaga, Taro Kishi, Nakao Iwata
BACKGROUND: There is uncertainty about the efficacy and tolerability of zonisamide for Parkinson's disease (PD). OBJECTIVE: We performed a meta-analysis of zonisamide treatment in PD patients who received antiparkinson drugs such as levodopa. METHODS: The primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, wearing-off time, and discontinuation rate due to all causes. Secondary outcome measures were UPDRS total and subscale scores; discontinuation rates due to adverse events, inefficacy, and death; and individual adverse events...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28130646/the-effect-of-mirtazapine-on-dopaminergic-psychosis-and-dyskinesia-in-the-parkinsonian-marmoset
#19
Adjia Hamadjida, Stephen G Nuara, Nicolas Veyres, Imane Frouni, Cynthia Kwan, Lamia Sid-Otmane, Mery-Jane Harraka, Jim C Gourdon, Philippe Huot
BACKGROUND: Parkinson's disease (PD) psychosis is encountered in as many as 50% of patients with advanced disease. Treatment options for PD psychosis are few. In fact, only clozapine and pimavanserin have shown efficacy in randomised controlled trials. Clinicians are often reluctant to prescribe the former, due to the risk of agranulocytosis, while the latter is not widely available yet. Because it is already clinically available and exhibits high affinity for serotonin 2A receptors, a target with which both clozapine and pimavanserin interact, we hypothesised that the anti-depressant mirtazapine might be effective to alleviate PD psychosis...
March 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28125927/statistical-methods-for-unidirectional-switch-designs-past-present-and-future
#20
Zhuozhao Zhan, Geertruida H de Bock, Edwin R van den Heuvel
Clinical trials may apply or use a sequential introduction of a new treatment to determine its efficacy or effectiveness with respect to a control treatment. The reasons for choosing a particular switch design have different origins. For instance, they may be implemented for ethical or logistic reasons or for studying disease-modifying effects. Large-scale pragmatic trials with complex interventions often use stepped wedge designs (SWDs), where all participants start at the control group, and during the trial, the control treatment is switched to the new intervention at different moments...
January 1, 2017: Statistical Methods in Medical Research
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