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Parkinson drugs trials

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https://www.readbyqxmd.com/read/27902767/towards-a-non-human-primate-model-of-alpha-synucleinopathy-for-development-of-therapeutics-for-parkinson-s-disease-optimization-of-aav1-2-delivery-parameters-to-drive-sustained-expression-of-alpha-synuclein-and-dopaminergic-degeneration-in-macaque
#1
James B Koprich, Tom H Johnston, Gabriela Reyes, Vanessa Omana, Jonathan M Brotchie
Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27869056/why-calpain-inhibitors-are-interesting-leading-compounds-to-search-for-new-therapeutic-options-to-treat-leishmaniasis
#2
Vitor Ennes-Vidal, Rubem Figueiredo Sadock Menna-Barreto, Marta Helena Branquinha, André Luis Souza Dos Santos, Claudia Masini D'Avila-Levy
Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials...
November 21, 2016: Parasitology
https://www.readbyqxmd.com/read/27866808/combined-beta-glucosylceramide-and-ambroxol-hydrochloride-in-patients-with-gaucher-related-parkinson-disease-from-clinical-observations-to-drug-development
#3
Yuval Ishay, Ari Zimran, Jeffrey Szer, Tama Dinur, Yaron Ilan, David Arkadir
Both patients with non-neuronopathic Gaucher disease (GD) and heterozygous GBA mutation carrier are at increased risk for Parkinson disease (PD). The risk for PD in these groups does not linearly increase with glucosylceramide (GC) accumulation or with acid β-glucocerebrosidase (GCase) activity. This observation, together with other clinical systemic observations raises the possibility that extra-cellular GC actually has beneficial, anti-inflammatory, properties. Based on this hypothesis, we suggest here that the administration of supplementary oral GC to GBA carriers at risk for PD may slow inflammatory-driven secondary neuronal death...
November 12, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27865667/lower-urinary-tract-symptoms-in-parkinson-s-disease-prevalence-aetiology-and-management
#4
REVIEW
Claire McDonald, Kristian Winge, David J Burn
Lower urinary tract symptoms (LUTS) are common in Parkinson's disease (PD), effecting 27-85% of patients with PD. Irritative symptoms predominate and urodynamic studies confirm high prevalence of detrusor overactivity in PD. LUTS are present early in PD and are more common in PD than in age matched controls. The assessment of LUTS in PD is complicated by coexisting bradykinesia and cognitive impairment. Although LUTS become more troublesome as PD progresses it remains unclear if LUTS severity correlates with motor symptoms and/or duration of PD...
November 1, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27859866/modeling-idiopathic-parkinson-disease-as-a-complex-illness-can-inform-incidence-risk-in-healthy-adults-the-pr-edigt-score
#5
Michael G Schlossmacher, Julianna J Tomlinson, Goncalo Santos, Bojan Shutinoski, Earl G Brown, Douglas Manuel, Tiago Mestre
Fifty-five years after the concept of dopamine replacement therapy was introduced, Parkinson disease (PD) remains an incurable neurological disorder. To date, no disease-modifying therapeutic has been approved. The inability to predict PD incidence risk in healthy adults is seen as one limitation in drug development, because by the time of clinical diagnosis >60% of dopamine neurons have been lost. We have designed an incidence prediction model founded on the concept that the pathogenesis of PD is similar to that of many disorders observed in ageing humans, i...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27830492/transcranial-magnetic-stimulation-for-the-assessment-of-neurodegenerative-disease
#6
REVIEW
Steve Vucic, Matthew C Kiernan
Transcranial magnetic stimulation (TMS) is a noninvasive technique that has provided important information about cortical function across an array of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and related extrapyramidal disorders. Application of TMS techniques in neurodegenerative diseases has provided important pathophysiological insights, leading to the development of pathogenic and diagnostic biomarkers that could be used in the clinical setting and therapeutic trials...
November 9, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27826740/calcium-channel-antagonists-as-disease-modifying-therapy-for-parkinson-s-disease-therapeutic-rationale-and-current-status
#7
Tara Swart, Michael J Hurley
Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated CaV1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease...
November 8, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27819412/harnessing-cerebrospinal-fluid-biomarkers-in-clinical-trials-for-treating-alzheimer-s-and-parkinson-s-diseases-potential-and-challenges
#8
REVIEW
Dana Kim, Young Sam Kim, Dong Wun Shin, Chang Shin Park, Ju Hee Kang
No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool...
October 2016: Journal of Clinical Neurology
https://www.readbyqxmd.com/read/27802242/effects-of-safinamide-on-pain-in-fluctuating-parkinson-s-disease-patients-a-post-hoc-analysis
#9
Carlo Cattaneo, Paolo Barone, Erminio Bonizzoni, Marco Sardina
BACKGROUND: Pain, a frequent non-motor symptom in Parkinson's Disease (PD), significantly impacts on quality of life. Safinamide is a new drug with dopaminergic and non-dopaminergic properties, approved in Europe as adjunct therapy to levodopa for the treatment of fluctuating PD patients. Results from two 24-month, double-blind, placebo-controlled studies demonstrated that safinamide has positive effects on both motor functions and quality of life in PD patients. OBJECTIVE: To investigate the effects of safinamide on pain management in PD patients with motor fluctuations using pooled data from studies 016 and SETTLE...
October 11, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27774496/parkinson-s-impulse-control-scale-for-the-severity-rating-of-impulse-control-behaviors-in-parkinson-s-disease-a-semistructured-clinical-assessment-tool
#10
David Okai, Sally Askey-Jones, Joel Mack, Anne Martin, Kallol Ray Chaudhuri, Michael Samuel, Anthony S David, Richard G Brown
BACKGROUND: Impulse-control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug-related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician-rated severity scale for the assessment of syndromal and subsyndromal forms of impulse-control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome)...
September 2016: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/27714426/chronic-administration-of-the-dopamine-d2-3-agonist-ropinirole-invigorates-performance-of-a-rodent-slot-machine-task-potentially-indicative-of-less-distractible-or-compulsive-like-gambling-behaviour
#11
Paul J Cocker, M Tremblay, S Kaur, Catharine A Winstanley
RATIONALE: Whilst dopamine agonist therapies can successfully manage the symptoms of diseases such as Parkinson's disease (PD), fibromyalgia and restless leg syndrome, they can also cause impulse control and addiction disorders such as gambling disorder (GD). These compulsive behaviours seriously undermine the utility of such treatments. OBJECTIVES: The objective of the study was to model this phenomenon using a rodent slot machine task (rSMT) in order to investigate the neurobiological basis underlying such behavioural changes...
October 6, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27713036/insulin-resistance-and-parkinson-s-disease-a-new-target-for-disease-modification
#12
REVIEW
D Athauda, T Foltynie
There is growing evidence that patients with Type 2 diabetes have an increased risk of developing Parkinson's disease and share similar dysregulated pathways suggesting common underlying pathological mechanisms. Historically insulin was thought solely to be a peripherally acting hormone responsible for glucose homeostasis and energy metabolism. However accumulating evidence indicates insulin can cross the blood-brain-barrier and influence a multitude of processes in the brain including regulating neuronal survival and growth, dopaminergic transmission, maintenance of synapses and pathways involved in cognition...
October 2016: Progress in Neurobiology
https://www.readbyqxmd.com/read/27686862/neural-stem-cell-tumorigenicity-and-biodistribution-assessment-for-phase-i-clinical-trial-in-parkinson-s-disease
#13
Ibon Garitaonandia, Rodolfo Gonzalez, Trudy Christiansen-Weber, Tatiana Abramihina, Maxim Poustovoitov, Alexander Noskov, Glenn Sherman, Andrey Semechkin, Evan Snyder, Russell Kern
Human pluripotent stem cells (PSC) have the potential to revolutionize regenerative medicine. However undifferentiated PSC can form tumors and strict quality control measures and safety studies must be conducted before clinical translation. Here we describe preclinical tumorigenicity and biodistribution safety studies that were required by the US Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) prior to conducting a Phase I clinical trial evaluating the safety and tolerability of human parthenogenetic stem cell derived neural stem cells ISC-hpNSC for treating Parkinson's disease (ClinicalTrials...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27665574/clinical-pharmacokinetics-and-pharmacodynamics-of-safinamide
#14
Thomas Müller, Paul Foley
The symptoms of Parkinson's disease (PD) reflect disruptions of a number of brain neurotransmitter systems of varying type and degree. Pharmacological agents with multiple neurochemical mechanisms of action are therefore promising candidates for countering these problems and providing comprehensive symptomatic relief for patients. The pharmacological profile of safinamide includes reversible monoamine oxidase B inhibition, blockage of voltage-dependent Na(+) channels, modulation of Ca(2+) channels, and inhibition of glutamate release...
September 24, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27664323/subacute-toxicity-evaluation-of-kr-33493-faf1-inhibitor-for-a-new-anti-parkinson-s-disease-agent-after-oral-administration-in-rats-and-dogs
#15
Jong-Woo Jeong, Changsun Yu, Jong-Hwa Lee, Kyoung-Sik Moon, Eunhee Kim, Sung-Eun Yoo, Tae-Sung Koo
KR33493, a newly developed FAS-associated factor 1 (FAF1) inhibitor for Parkinson's disease, is being evaluated in a Phase I clinical trial. In the present study, the subchronic toxicity of KR33493 in Sprague-Dawley (SD) rats and beagle dogs was investigated at various oral doses for 28 and 14 days, respectively. During the study, food consumption, body weights, organ weights, gross findings, and mortality were examined; and ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, histopathology, and toxicokinetics were performed...
November 2016: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/27660217/cholinergic-and-dopaminergic-alterations-in-nigrostriatal-neurons-are-involved-in-environmental-enrichment-motor-protection-in-a-mouse-model-of-parkinson-s-disease
#16
Willyan Franco Hilario, Alice Laschuk Herlinger, Lorena Bianchine Areal, Lívia Silveira de Moraes, Tamara Andrea Alarcon Ferreira, Tassiane Emanuelle Servane Andrade, Cristina Martins-Silva, Rita Gomes Wanderley Pires
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, being characterized by dopaminergic neurodegeneration of substantia nigra pars compacta. PD pharmacotherapy has been based on dopamine replacement in the striatum with the dopaminergic precursor 3,4-dihydroxyphenylalanine (L-DOPA) and/or with dopaminergic agonists, alongside anticholinergic drugs in order to mitigate the motor abnormalities. However, these practices neither prevent nor stop the progression of the disease...
September 22, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27639815/orthostatic-hypotension-predicts-motor-decline-in-early-parkinson-disease
#17
Vikas Kotagal, Christina Lineback, Nicolaas I Bohnen, Roger L Albin
BACKGROUND: Orthostatic hypotension is increasingly reported as a risk factor for development of late-stage disease features in Parkinson disease (PD). Less is known about its significance in individuals with early PD who are often targeted for neuroprotective trials. METHODS: Using data from the CALM-PD trial (n = 275), we explored whether early orthostatic hypotension predicts a decline in the Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living) or UDPRS III (motor) score after 102 weeks...
November 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27618808/freezing-festination-during-motor-tasks-in-early-stage-parkinson-s-disease-a-prospective-study
#18
Arnaud Delval, Mélanie Rambour, Céline Tard, Kathy Dujardin, David Devos, Séverine Bleuse, Luc Defebvre, Caroline Moreau
BACKGROUND: Parkinsonian patients have a tendency to speed up during repetitive motor tasks (festination) and to experience sudden motor blocks (freezing). In this article, we prospectively studied the appearance and progression of these phenomena in 30 early-stage PD patients. METHODS: A total of 30 controls and early-stage PD patients were assessed in the "off-drug" condition at baseline and 2 years later. Freezing of gait was evaluated using a standardized gait trajectory with the usual triggers...
September 13, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27616425/gene-therapy-for-parkinson-s-disease-disease-modification-by-gdnf-family-of-ligands
#19
Deniz Kirik, Erik Cederfjäll, Glenda Halliday, Åsa Petersén
Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor l-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain...
September 8, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27599671/clinical-pharmacology-review-of-opicapone-for-the-treatment-of-parkinson-s-disease
#20
Margherita Fabbri, Mario M Rosa, Joaquim J Ferreira
Two catechol-O-methyl transferase inhibitors are currently used as add-on therapy to levodopa for the amelioration of end-of-dose motor fluctuations in Parkinson's disease patients: entacapone, which has moderate efficacy and requires multiple dosing, and tolcapone, which has a poor safety profile. Opicapone (OPC) is a novel, long-acting, peripherally selective, once daily, third-generation catechol-O-methyl transferase inhibitor. Two Phase III clinical trials demonstrated OPC efficacy in reducing OFF-time by an average of about 60 min daily compared with placebo, without increasing ON-time with troublesome dyskinesias, with a good drug safety profile...
October 2016: Neurodegenerative Disease Management
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