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Parkinson's treatment

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46 papers 1000+ followers
By Faye Kehler Family Physician and GP Anesthetist since 1987 interested in all aspects of Medicine
Markus Mandler, Elvira Valera, Edward Rockenstein, Harald Weninger, Christina Patrick, Anthony Adame, Radmila Santic, Stefanie Meindl, Benjamin Vigl, Oskar Smrzka, Achim Schneeberger, Frank Mattner, Eliezer Masliah
Immunotherapeutic approaches are currently in the spotlight for their potential as disease-modifying treatments for neurodegenerative disorders. The discovery that α-synuclein (α-syn) can transmit from cell to cell in a prion-like fashion suggests that immunization might be a viable option for the treatment of synucleinopathies. This possibility has been bolstered by the development of next-generation active vaccination technology with short peptides-AFFITOPEs(®) (AFF)- that do not elicit an α-syn-specific T cell response...
2014: Acta Neuropathologica
Karl Kieburtz, Barbara C Tilley, Jordan J Elm, Debra Babcock, Robert Hauser, G Webster Ross, Alicia H Augustine, Erika U Augustine, Michael J Aminoff, Ivan G Bodis-Wollner, James Boyd, Franca Cambi, Kelvin Chou, Chadwick W Christine, Michelle Cines, Nabila Dahodwala, Lorelei Derwent, Richard B Dewey, Katherine Hawthorne, David J Houghton, Cornelia Kamp, Maureen Leehey, Mark F Lew, Grace S Lin Liang, Sheng T Luo, Zoltan Mari, John C Morgan, Sotirios Parashos, Adriana Pérez, Helen Petrovitch, Suja Rajan, Sue Reichwein, Jessie Tatsuno Roth, Jay S Schneider, Kathleen M Shannon, David K Simon, Tanya Simuni, Carlos Singer, Lewis Sudarsky, Caroline M Tanner, Chizoba C Umeh, Karen Williams, Anne-Marie Wills
IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease...
February 10, 2015: JAMA: the Journal of the American Medical Association
Dan Lindholm, Johanna Mäkelä, Valentina Di Liberto, Giuseppa Mudò, Natale Belluardo, Ove Eriksson, Mart Saarma
Parkinson's disease (PD is a progressive neurological disorder characterized by the degeneration and death of midbrain dopamine and non-dopamine neurons in the brain leading to motor dysfunctions and other symptoms, which seriously influence the quality of life of PD patients. The drug L-dopa can alleviate the motor symptoms in PD, but so far there are no rational therapies targeting the underlying neurodegenerative processes. Despite intensive research, the molecular mechanisms causing neuronal loss are not fully understood which has hampered the development of new drugs and disease-modifying therapies...
April 2016: Cellular and Molecular Life Sciences: CMLS
Kevin M Biglan, David Oakes, Anthony E Lang, Robert A Hauser, Karen Hodgeman, Brittany Greco, Jillian Lowell, Rebecca Rockhill, Ira Shoulson, Charles Venuto, Diony Young, Tanya Simuni
OBJECTIVE: To describe the rationale for a novel study design and baseline characteristics of a disease-modifying trial of isradipine 10 mg daily in early Parkinson disease (PD). METHODS: STEADY-PDIII is a 36-month, Phase 3, parallel group, placebo-controlled study of the efficacy of isradipine 10 mg daily in 336 participants with early PD as measured by the change in the Unified Parkinson Disease Rating Scale (UPDRS) Part I-III score in the practically defined ON state...
June 2017: Annals of Clinical and Translational Neurology
Michael A Schwarzschild, Alberto Ascherio, M Flint Beal, Merit E Cudkowicz, Gary C Curhan, Joshua M Hare, D Craig Hooper, Karl D Kieburtz, Eric A Macklin, David Oakes, Alice Rudolph, Ira Shoulson, Marsha K Tennis, Alberto J Espay, Maureen Gartner, Albert Hung, Grace Bwala, Richard Lenehan, Elmyra Encarnacion, Melissa Ainslie, Richard Castillo, Daniel Togasaki, Gina Barles, Joseph H Friedman, Lisa Niles, Julie H Carter, Megan Murray, Christopher G Goetz, Jeana Jaglin, Anwar Ahmed, David S Russell, Candace Cotto, John L Goudreau, Doozie Russell, Sotirios Andreas Parashos, Patricia Ede, Marie H Saint-Hilaire, Cathi-Ann Thomas, Raymond James, Mark A Stacy, Julia Johnson, Lisa Gauger, J Antonelle de Marcaida, Sheila Thurlow, Stuart H Isaacson, Lisbeth Carvajal, Jayaraman Rao, Maureen Cook, Charlise Hope-Porche, Lauren McClurg, Daniela L Grasso, Robert Logan, Constance Orme, Tori Ross, Alicia F D Brocht, Radu Constantinescu, Saloni Sharma, Charles Venuto, Joseph Weber, Ken Eaton
IMPORTANCE: Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). OBJECTIVE: To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. DESIGN, SETTING, AND PARTICIPANTS: The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States...
February 2014: JAMA Neurology
(no author information available yet)
BACKGROUND: Treatment with rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, improves symptoms of early Parkinson disease (PD). Preclinical studies suggest that this compound may also modify the progression of PD. OBJECTIVE: To compare the effects of early and later initiation of rasagiline on progression of disability in patients with PD. DESIGN: Double-blind, parallel-group, randomized, delayed-start clinical trial...
April 2004: Archives of Neurology
(no author information available yet)
Isradipine, a dihydropyridine calcium channel antagonist, has been shown to be neuroprotective in animal models of Parkinson's disease (PD). To establish a dosage of isradipine controlled-release (CR) that is tolerable and demonstrates preliminary efficacy for use in a future pivotal efficacy trial a Phase 2, randomized, double-blind, parallel group trial (Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease [STEADY-PD]) was undertaken in subjects with early PD not requiring dopaminergic therapy (dopamine agonists or levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching placebo daily...
November 2013: Movement Disorders: Official Journal of the Movement Disorder Society
C Rodriguez-Blazquez, M J Forjaz, B Frades-Payo, J de Pedro-Cuesta, P Martinez-Martin
BACKGROUND AND PURPOSE: Autonomic dysfunction is common in Parkinson's disease (PD) and causes a great impact in health-related quality of life (HRQL) and functional status of patients. This study is the first independent validation of the Scales for Outcomes in PD-Autonomic (SCOPA-AUT). METHODS: In an observational, cross-sectional study (ELEP Study), 387 PD patients were assessed using, in addition to the SCOPA-AUT, the Hoehn and Yahr staging, SCOPA-Motor, SCOPA-Cognition, Cumulative Illness Rating Scale-Geriatrics, modified Parkinson Psychosis Rating Scale, Clinical Impression of Severity Index for PD, Hospital Anxiety and Depression Scale, SCOPA-Sleep, SCOPA-Psychosocial, pain and fatigue visual analogue scales, and EQ-5D...
February 2010: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Kyle B Fraser, Ashlee B Rawlins, Rachel G Clark, Roy N Alcalay, David G Standaert, Nianjun Liu, Andrew B West
BACKGROUND: Mutations in Leucine-rich repeat kinase 2 (LRRK2) enhance levels of the autophosphorylated LRRK2 protein and are the most common known cause of inherited Parkinson's disease (PD). LRRK2 has been further implicated in susceptibility to idiopathic PD in genetic association studies. OBJECTIVE: The objective of this study was to compare autophosphorylated Ser(P)-1292 LRRK2 levels from biobanked urine samples with clinical data in PD patients and controls...
October 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Valerie Voon, T Celeste Napier, Michael J Frank, Veronique Sgambato-Faure, Anthony A Grace, Maria Rodriguez-Oroz, Jose Obeso, Erwan Bezard, Pierre-Olivier Fernagut
Dopaminergic medications used in the treatment of patients with Parkinson's disease are associated with motor and non-motor behavioural side-effects, such as dyskinesias and impulse control disorders also known as behavioural addictions. Levodopa-induced dyskinesias occur in up to 80% of patients with Parkinson's after a few years of chronic treatment. Impulse control disorders, including gambling disorder, binge eating disorder, compulsive sexual behaviour, and compulsive shopping occur in about 17% of patients with Parkinson's disease on dopamine agonists...
March 2017: Lancet Neurology
Robert G Holloway, Ira Shoulson, Stanley Fahn, Karl Kieburtz, Anthony Lang, Kenneth Marek, Michael McDermott, John Seibyl, William Weiner, Bruno Musch, Cornelia Kamp, Mickie Welsh, Aileen Shinaman, Rajesh Pahwa, Lynn Barclay, Jean Hubble, Peter LeWitt, Janis Miyasaki, Oksana Suchowersky, Mark Stacy, David S Russell, Blair Ford, John Hammerstad, David Riley, David Standaert, Frederick Wooten, Stewart Factor, Joseph Jankovic, Farah Atassi, Roger Kurlan, Michel Panisset, Ali Rajput, Robert Rodnitzky, Cliff Shults, Giselle Petsinger, Cheryl Waters, Ronald Pfeiffer, Kevin Biglan, Leona Borchert, Amy Montgomery, Laura Sutherland, Carolyn Weeks, Maryan DeAngelis, Elspeth Sime, Susan Wood, Carol Pantella, Mary Harrigan, Barbara Fussell, Sandra Dillon, Barbara Alexander-Brown, Pamela Rainey, Marsha Tennis, Elke Rost-Ruffner, Diane Brown, Sharon Evans, Debra Berry, Jean Hall, Theresa Shirley, Judith Dobson, Deborah Fontaine, Brenda Pfeiffer, Alicia Brocht, Susan Bennett, Susan Daigneault, Karen Hodgeman, Carolynn O'Connell, Tori Ross, Karen Richard, Arthur Watts
BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter, parallel-group, double-blind, randomized controlled trial...
July 2004: Archives of Neurology
Claudia Trenkwalder, K Ray Chaudhuri, Pedro J García Ruiz, Peter LeWitt, Regina Katzenschlager, Friederike Sixel-Döring, Tove Henriksen, Ángel Sesar, Werner Poewe, Mary Baker, Andres Ceballos-Baumann, Günther Deuschl, Sophie Drapier, Georg Ebersbach, Andrew Evans, Hubert Fernandez, Stuart Isaacson, Teus van Laar, Andrew Lees, Simon Lewis, Juan Carlos Martínez Castrillo, Pablo Martinez-Martin, Per Odin, John O'Sullivan, Georgios Tagaris, Karoline Wenzel
Extensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuous infusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment...
September 2015: Parkinsonism & related Disorders
(no author information available yet)
BACKGROUND: Rasagiline (n-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD). OBJECTIVE: To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations. DESIGN: Multicenter, randomized, placebo-controlled, double-blind, parallel-group study. PATIENTS: Parkinson disease patients (N = 472) with at least 21/2 hours of daily "off" (poor motor function) time, despite optimized treatment with other anti-PD medications...
February 2005: Archives of Neurology
(no author information available yet)
OBJECTIVE: To compare the long-term outcomes of subjects initially treated with pramipexole dihydrochloride with those of subjects initially treated with levodopa in the Comparison of the Agonist Pramipexole With Levodopa on Motor Complications of Parkinson's Disease (CALM-PD) trial. DESIGN: Up to 2 years of open extended follow-up of the CALM-PD subjects. SETTING: Academic movement disorders clinics at 22 sites in the United States and Canada...
May 2009: Archives of Neurology
Un Jung Kang, Peggy Auinger
OBJECTIVE: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. METHODS: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks...
April 10, 2012: Neurology
(no author information available yet)
BACKGROUND: A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. METHODS: Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo...
August 2015: Lancet Neurology
Herbert Y Meltzer, Roger Mills, Stephen Revell, Hilde Williams, Ann Johnson, Daun Bahr, Joseph H Friedman
Psychotic symptoms occur in up to 40% of patients with Parkinson's disease (PD). Clozapine and quetiapine, two atypical antipsychotic drugs, at doses markedly lower than those effective in schizophrenia, which, nevertheless, still cause sedation, hypotension, and other side effects, are widely used to treat psychotic symptoms in patients with PD psychosis (PDP), although quetiapine has never been shown to be effective in a placebo-controlled study. The demonstrated efficacy of clozapine in PDP has been attributed to serotonin (5-HT(2A)) receptor blockade...
March 2010: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Hélène Pouclet, Thibaud Lebouvier, Emmanuel Coron, Stanislas Bruley des Varannes, Tiphaine Rouaud, Monica Roy, Michel Neunlist, Pascal Derkinderen
We have shown that routine biopsies of the ascending colon obtained at colonoscopy allow the detection of Lewy neurites (LN) in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. Although colonoscopy is a relatively safe procedure, it requires colon preparation and anesthesia. The present study was therefore undertaken to evaluate whether descending colon and rectal biopsies that are obtainable by rectosigmoidoscopy allow the detection of Lewy pathology in the ENS. A total of 9 controls and 26 PD patients were included and analyzed...
January 2012: Neurobiology of Disease
Justin J Wright, Peter D Goodnight, Matthew D McEvoy
Loss of dopaminergic neurons from the substantia nigra characterizes the classical pathology of Parkinson's disease, but persistent activation of N-methyl-D-aspartate receptors is also a major component. During difficult airway management in a patient with advanced Parkinson's disease, the use of low-dose (20 mg) i.v. ketamine resulted in complete abolition of severe tremor and dysarthria. This led to the current case report in which low-dose ketamine was used for preoperative sedation and dyskinesia attenuation...
March 2009: Anesthesia and Analgesia
Jack J Chen, Jayne R Wilkinson
Rasagiline is an irreversible monoamine oxidase type B (MAO-B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO-A), but not MAO-B, poses a risk of the "cheese effect," a hypertensive response to excess dietary tyramine, a biogenic sympathomimetic amine. Tyramine challenge studies, conducted to characterize rasagiline selectivity for the MAO-B enzyme and tyramine sensitivity, demonstrate that rasagiline, when used at the recommended dose, is selective for MAO-B and is not associated with heightened tyramine sensitivity...
May 2012: Journal of Clinical Pharmacology
2016-02-20 01:29:27
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