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Parkinson drugs trials

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https://www.readbyqxmd.com/read/28303913/multiple-system-atrophy-insights-into-a-rare-and-debilitating-movement-disorder
#1
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
#2
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
#3
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
#4
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
#5
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...
February 28, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28124620/monoamine-oxidase-b-inhibitors-in-parkinson-s-disease
#12
Livia Dézsi, László Vécsei
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. OBJECTIVE: To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials...
January 24, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28123400/six-psychotropics-for-pre-symptomatic-early-alzheimer-s-mci-parkinson-s-and-huntington-s-disease-modification
#13
REVIEW
Edward C Lauterbach
The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28103749/clinical-practice-with-anti-dementia-drugs-a-revised-third-consensus-statement-from-the-british-association-for-psychopharmacology
#14
John T O'Brien, Clive Holmes, Matthew Jones, Roy Jones, Gill Livingston, Ian McKeith, Peter Mittler, Peter Passmore, Craig Ritchie, Louise Robinson, Elizabeth L Sampson, John-Paul Taylor, Alan Thomas, Alistair Burns
The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B)...
February 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28095073/preclinical-and-potential-applications-of-common-western-herbal-supplements-as-complementary-treatment-in-parkinson-s-disease
#15
Luke A Morgan, Oliver Grundmann
Parkinson's disease (PD) is a neurological disorder with a complex pathological etiology, which is not fully understood. Progression of PD may be the result of a buildup of iron in the substantia nigra, microglia-mediated neuroinflammation, dysfunctional mitochondria, or abnormal protein handling. Dopamine is the main neurotransmitter affected, but as the disease progresses, a decrease in all the brain's biogenic amines occurs. Current medication used in the treatment of PD aims to prevent the breakdown of dopamine or increase dopaminergic neurotransmission in the central nervous system...
July 4, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28025940/a-mini-review-on-the-chemistry-and-neuroprotective-effects-of-silymarin
#16
Kasi Pandima Devi, Dicson Sheeja Malar, Nady Braidy, Seyed Mohammad Nabavi, Seyed Fazel Nabavi
The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such Alzheimer's and Parkinson's Disease and cerebral ischemia for over 2000 years. The neuroprotective effects conferred by silymarin include modulation of various antioxidant mechanisms, and several kinases involved in cell signaling pathways, inhibition of the inflammatory response generated during neurodegeneration, neurotropic effects, regulation of neurotransmitters and inhibition of apoptosis...
December 27, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27999408/cyclodextrins-as-emerging-therapeutic-tools-in-the-treatment-of-cholesterol-associated-vascular-and-neurodegenerative-diseases
#17
REVIEW
Caroline Coisne, Sébastien Tilloy, Eric Monflier, Daniel Wils, Laurence Fenart, Fabien Gosselet
Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics...
December 20, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27979722/apomorphine-pharmacological-properties-and-clinical-trials-in-parkinson-s-disease
#18
Peter Jenner, Regina Katzenschlager
Apomorphine is often considered an archetypal dopamine agonist used in the treatment of Parkinson's disease (PD). However, it can be clearly differentiated from most other commonly used dopamine agonists on the basis of its pharmacology and on its unique clinical profile. Like levodopa and dopamine, apomorphine acts as a potent, direct and broad spectrum dopamine agonist activating all dopamine receptor subtypes. It also has affinity for serotonin receptors, and α-adrenergic receptors. Apomorphine is usually titrated to a dose that provides an equivalent antiparkinsonian response to that provided by levodopa, and its subcutaneous delivery allows a rapid onset of action, usually within 7-10 min...
December 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27965247/can-commonly-prescribed-drugs-be-repurposed-for-the-prevention-or-treatment-of-alzheimer-s-and-other-neurodegenerative-diseases-protocol-for-an-observational-cohort-study-in-the-uk-clinical-practice-research-datalink
#19
Venexia M Walker, Neil M Davies, Tim Jones, Patrick G Kehoe, Richard M Martin
INTRODUCTION: Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis...
December 13, 2016: BMJ Open
https://www.readbyqxmd.com/read/27917685/phosphodiesterase-10-inhibitors-in-clinical-development-for-cns-disorders
#20
Hugo Geerts, Athan Spiros, Patrick Roberts
Phosphodiesterase 10 inhibitors (PDE10-I), are conceptually attractive drugs with a potential great therapeutic window as their enriched striatal localization may likely stimulate D1R and reduce D2R downstream effects. However, so far selective PDE10-I with efficacy in animal models have not shown benefit in clinical trials and unexpectedly revealed a substantial dyskinesia motor side-effect. Areas covered: This paper reviews the underlying biological rationale of PDE10 as a target in schizophrenia, Parkinson's and Huntington's disease based on peer-reviewed published articles, the status of the different PDE10-I in clinical development for various CNS indications and explores possible reasons for the clinical trial failures and translational disconnect...
December 10, 2016: Expert Review of Neurotherapeutics
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