Therapies in Parkinsonʼs disease

Jankovic, Joseph; Poewe, Werner

doi:10.1097/wco.0b013e3283542fc2

Cited by 186 publications

(96 citation statements)

References 115 publications

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“…They might be more prone to the higher usage of dopaminergic treatment in order to reduce their parkinsonian symptoms than older patients as a result of having more commitments concerning their employment status and families than older patients. Levodopa may be postponed in patients who are not troubled by their PD‐related motor symptoms and in patients with young‐onset PD who are at the highest risk for developing levodopa‐related complications (Jankovic & Poewe, 2012). At the same time, the possibility of the different effects of dyskinesias and motor fluctuations on quality of life should be taken into account.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with motor complications in Parkinson's disease

et al. 2017

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ObjectivesLevodopa is the most effective therapy for treating Parkinson's disease (PD); however, side effects such as dyskinesias and motor fluctuations may occur after some years of its usage. The aims of this study were to assess the frequency of and factors associated with motor complications among PD patients on levodopa treatment.MethodsIn a cross‐sectional study carried out in 2010–2013, clinical data and treatment details were collected. Logistic regression expressed by odd ratios (OR) and 95% confidence intervals (CI) was conducted to examine the effects of several independent variables on the occurrence of motor complications.ResultsA total of 455 patients were enrolled, among whom 374 were on levodopa. Analysis was performed in 328 patients whose exact duration of levodopa treatment was known. Among patients included in the analysis, 25.9% experienced motor complications; of these, 21% had dyskinesias and 20.1% had motor fluctuations. Based on logistic regression, statistically significant factors associated with the occurrence of motor complications were younger age at onset of the disease, higher levodopa equivalent daily dose (LEDD), shorter time to levodopa initiation, and akinetic‐rigid dominant phenotype of PD.ConclusionsThis study suggests that postponing the start of levodopa therapy and maintaining low daily doses of levodopa might reduce the risk of motor complications. Our results confirm that due to higher risk of motor complications, effectively treating patients with akinetic‐rigid dominant phenotype of PD might be more challenging than for patients whose dominant symptom is tremor.

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Section: Discussionmentioning

confidence: 99%

Factors associated with motor complications in Parkinson's disease

et al. 2017

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“…Ropinirole is a long-acting, non-ergot DA agonist that has a potential to provide more continuous DAergic stimulation [10]. Ropinirole continuous infusion with subcutaneous administration in MPTP-treated marmoset can reverse motor deficits and cause less dyskinesia when compared with the orally administered form [128].…”

Section: Continuous Subcutaneous Infusion Of Ropinirole Via Osmotic Mmentioning

confidence: 99%

“…Even though levodopa is considered the gold standard in the treatment of motor symptoms of PD, it is often associated with acute and chronic adverse events, particularly motor fluctuations and dyskinesia [10]. Many other therapeutic options have their own limitations.…”

Section: Introductionmentioning

confidence: 99%

Animal Models of Parkinson's Disease: A Gateway to Therapeutics?

Sayana

Jankovic

2014

Neurotherapeutics

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Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.

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“…Вместе с тем анализ пациентов, которые по окончании исследования получали леводопу вместе с се-легилином на протяжении 7 лет, показал снижение тем-пов прогрессирования заболевания, уменьшение длитель-ности периодов «выключения», реже встречались фено-мен «включения-выключения», застывания при ходьбе, по сравнению с пациентами, которым селегилин был за-менен на плацебо через 5 лет терапии. Однако дискинезии в группе селегилина регистрировались чаще [20]. Подоб-ные результаты были получены в Скандинавском иссле-довании, в котором было показано благоприятное влия-ние селегилина в плане назначения леводопы и долго-срочного прогноза [32].…”

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“…Требуется более длительный период наблюдения, а также включение па-циентов с развернутой стадией болезни, что может по-мочь отдифференцировать симптоматический эффект от нейропротективного при более высоких дозах разагилина. В октябре 2011 г. FDA (the US Food and Drug Administration Advisory Committee) по результатам исследования TEMPO и ADAGIO признал доказательства модифициру-ющего эффекта разагилина недостаточными [20].…”

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Oxidative stress and Parkinson’s disease: mechanisms and perspectives of treatment

Katunina

Titova

Малыхина

et al. 2015

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Процесс образования свободных радикалов относит-ся к универсальным механизмам жизнедеятельности лю-бой живой клетки. Их основным источником является процесс трансформации кислорода в митохондриях. По-ступающий в клетку кислород подвергается полному вос-становлению до воды. Однако в процессе аэробного мета-болизма при неполном восстановлении кислорода в каче-стве промежуточных продуктов образуются свободные радикалы (СР). Они представляют собой различные по атомному составу химические вещества, общей особенно-стью которых является наличие неспаренного электрона на одной из их орбит. В результате этого СР являются не-стабильными веществами, обладающими высокой хими-ческой активностью. Свободные радикалы при контроли-руемом образовании играют важную физиологическую роль: регуляция сосудистого тонуса, проведение возбуж-дения, участие в реакциях воспаления, механизмах репа-рации, элиминации отживших клеток [6,12,43]. В то же время избыточное образование СР ассоциируется с пато-логическими процессами. Интенсификация свободнора-дикальных процессов в организме может быть вызвана как усилением образования активных форм кислорода (АФК), свободных радикалов и низкомолекулярных эн-догенных проокcидантов, так и снижением эффективно-сти действия биологических систем утилизации и деток-сикации АФК и СР. Образование СР могут провоциро-вать различные процессы, сопровождающие жизнедея-тельность организма: стрессы, ионизирующее излучение, токсины и т.д. СР участвуют в патогенезе большого коли-чества заболеваний -ишемии, сахарного диабета, череп-но-мозговой травмы, онкологии, атеросклероза, катарак-ты, преждевременного старения, болезни Паркинсона (БА), болезни Альцгеймера, хореи Гентингтона [14, 26, 44].

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Therapies in Parkinsonʼs disease

Cited by 186 publications

References 115 publications

Factors associated with motor complications in Parkinson's disease

Factors associated with motor complications in Parkinson's disease

Animal Models of Parkinson's Disease: A Gateway to Therapeutics?

Oxidative stress and Parkinson’s disease: mechanisms and perspectives of treatment

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