scholarly journals Therapeutic Potential of Pluripotent Stem Cell-derived Dopaminergic Progenitors in Parkinson's Disease: A Systematic Review Protocol

2020 ◽  
Author(s):  
Aliasghar Karimi ◽  
Mitra Elmi ◽  
Zahra Shiri ◽  
Hossein Baharvand
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Substantia Nigra Pars Compacta ◽  
Therapeutic Effects ◽  
Promising Alternative

Abstract Background: Parkinson's disease (PD) is the second most common age-dependent neurodegenerative disease that causes motor and cognitive disabilities. This disease is associated with a loss of dopamine content within the putamen, which stems from the degeneration of dopaminergic (DA) neurons in the Substantia Nigra pars Compacta (SNc). Several approved drugs are available that can effectively treat symptoms of PD. However, long-term medical management is often complicated and does not delay or halt disease progression. Alternatively, cell replacement strategies can address these shortcomings and provide dopamine where it is needed. Although using human pluripotent stem cells (hPSCs) for treatment of PD is a promising alternative, no consensus in the literature pertains to efficacy concerns of hPSC-based therapy for PD. This systematic review aims to investigate the efficacy of hPSC-derived DA progenitor transplantation to treat PD in preclinical animal models.Methods: This is a systematic review of preclinical studies in animal models of PD. We intend to use the following databases as article sources: MEDLINE (via PubMed), Web of Science, and SCOPUS without any restrictions on language or publication status for all related articles published until the end of 2019. Rescue of motor deficits is defined as the primary outcome, while histological and imaging data comprise the secondary outcomes. Two independent reviewers will select the titles and abstracts, extract data from qualifying studies, and assess the risk of bias by using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. The standardized mean difference (SMD) will be calculated to determine the efficacy of the treatment, with 95% confidence intervals (95% CI). The heterogeneity between studies will be calculated by "I2 inconsistency of values and Cochran's Q statistical test", where I2 > 50% and/or p < 0.10 suggest high heterogeneity. Meta-analyses of random effects will be run when appropriate.Discussion: This study will present an overview of preclinical research on hPSCs and their therapeutic effects in PD animal models. This systematic review will point out the strengths and limitations of studies in the current literature while encouraging the funding of new studies by public health managers and governmental bodies.

scholarly journals Therapeutic potential of pluripotent stem cell-derived dopaminergic progenitors in Parkinson’s disease: a systematic review protocol

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Aliasghar Karimi ◽  
Mitra Elmi ◽  
Zahra Shiri ◽  
Hossein Baharvand
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Risk Of Bias ◽  
Substantia Nigra Pars Compacta ◽  
Therapeutic Effects ◽  
Preclinical Studies ◽  
Promising Alternative ◽  
Rotation Test

Abstract Background Parkinson’s disease (PD) is the second most common age-dependent neurodegenerative disease that causes motor and cognitive disabilities. This disease is associated with a loss of dopamine content within the putamen, which stems from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Several approved drugs are available that can effectively treat symptoms of PD. However, long-term medical management is often complicated and does not delay or halt disease progression. Alternatively, cell replacement strategies can address these shortcomings and provide dopamine where it is needed. Although using human pluripotent stem cells (hPSCs) for treatment of PD is a promising alternative, no consensus in the literature pertains to efficacy concerns of hPSC-based therapy for PD. This systematic review aims to investigate the efficacy of primate PSC-derived DA progenitor transplantation to treat PD in preclinical studies. Methods This is a systematic review of preclinical studies in animal models of PD. We intend to use the following databases as article sources: MEDLINE (via PubMed), Web of Science, and SCOPUS without any restrictions on language or publication status for all related articles published until the end of April 2021. Two independent reviewers will select the titles and abstracts, extract data from qualifying studies, and assess the risk of bias using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Apomorphine-induced rotation test (APO-IR) and amphetamine-induced rotation test (AMP-IR) are defined as the primary outcomes. The standardized mean difference (SMD) by Hedges’ g method (r) and odds ratio (OR) and related 95% confidence interval (CI) will be calculated to determine the size effect of the treatment. The heterogeneity between studies will be calculated by “I2 inconsistency of values and Cochran’s Q statistical test,” where I2 > 50% and/or p < 0.10 suggests high heterogeneity. Meta-analyses of random effects will be run when appropriate. Discussion This study will present an overview of preclinical research on PSCs and their therapeutic effects in PD animal models. This systematic review will point out the strengths and limitations of studies in the current literature while encouraging the funding of new studies by public health managers and governmental bodies.

scholarly journals Does Caffeine Consumption Affect the Symptoms of Parkinson’s Disease? A Systematic Review of Clinical Trials

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Anita Reyhanifard ◽  
Sarvin Sanaie ◽  
Mojgan Mirghafurvand ◽  
Sama Rahnemayan ◽  
Arezoo Fathalizadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Assessment Tool ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Cochrane Library

Objectives: This systematic review of the literature was carried out to see whether coffee consumption could affect Parkinson’s disease (PD) symptoms. Methods: Randomized controlled trials (RCTs), crossover studies, and quasi-experimental studies were assessed to evaluate the effect of caffeine on PD. The databases including Medline/PubMed, ProQuest, Embase, Cochrane Library, and ClinicalTrials.gov were systematically searched. The Cochrane Collaboration’s tool for assessing the risk of bias in randomized clinical trials and the Cochrane risk of bias assessment tool for non-randomized studies of interventions (ROBINS-I) were used to assess the quality of RCTs and non-randomized clinical trials, respectively. A meta-analysis of the results was not possible because of reporting different outcomes. Results: Four papers were included in this study. Only one study reported the significant effect of caffeine on ESS and UPDRS. Another study observed no significant effect of caffeine on ESS during three- and six-week interventions. However, a significant reduction in ESS scores in the sixth week was reported after excluding four protocol violations. This study reported that the UPDRS score reduced in the third week, but significant changes were observed after six weeks. The other two studies did not show a significant effect of caffeine on ESS and UPDRS. Conclusions: Since a meta-analysis was not conducted, there was insufficient evidence to evaluate the effect of caffeine on PD. Thus, it is recommended to conduct more well-designed RCTs with a larger sample size to assess the effect of caffeine on PD.

The use of eHealth to promote physical activity in people living with Parkinson’s disease: A systematic review

2021 ◽  
pp. 1-14
Author(s):  
Adam McDermott ◽  
Ciaran Haberlin ◽  
Jonathan Moran
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Of Bias ◽  
Attrition Rate ◽  
Medical Subject Headings ◽  
Eligibility Criteria ◽  
Ehealth Intervention ◽  
High Level

BACKGROUND: People living with Parkinson’s disease (PD) are less active than healthy individuals. Ehealth is an emerging concept in healthcare which presents opportunities to promote physical activity (PA) in people with PD. The aim of this systematic review was to explore the effectiveness of ehealth in the promotion of PA in people living with PD. METHODS: Suitable articles were searched for using EMBASE, PsychInfo, Web of Science and OVID Medline databases using a combination of keywords and medical subject headings. Articles were included if they described an ehealth intervention designed to promote PA in people living with PD. Two reviewers screened studies for suitability and extracted data. Risk of bias was assessed using the Cochrane risk of bias 2 tool and the Downs and Black risk of bias checklist. Due to the heterogeneity of studies, a narrative synthesis of study interventions and results was completed rather than a quantitative analysis. RESULTS: 1449 articles were screened. Four studies met the eligibility criteria which included 652 participants. Web and mobile applications were used to design the PA interventions. PA levels were measured using self-reported questionnaires, Fitbits, activity monitors and accelerometers. Three of the studies reported improvements in aspects of PA. However, this was not consistently reported in all study participants. No adverse effects, a high level of enjoyment and a relatively low attrition rate (∼12.5%) were reported. CONCLUSION: Ehealth is a safe and feasible intervention to promote PA in this population. It is unclear whether ehealth is effective at promoting PA in people with PD. Keywords:

scholarly journals The effects of transcranial direct current stimulation on gait in patients with Parkinson’s disease: a systematic review

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Fateme Pol ◽  
Mohammad Ali Salehinejad ◽  
Hamzeh Baharlouei ◽  
Michael A. Nitsche
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Randomized Clinical Trials ◽  
Cortical Excitability ◽  
Experimental Studies ◽  
Gait Rehabilitation ◽  
Direct Current Stimulation

Abstract Background Gait problems are an important symptom in Parkinson’s disease (PD), a progressive neurodegenerative disease. Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention that can modulate cortical excitability of the gait-related regions. Despite an increasing number of gait-related tDCS studies in PD, the efficacy of this technique for improving gait has not been systematically investigated yet. Here, we aimed to systematically explore the effects of tDCS on gait in PD, based on available experimental studies. Methods Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, PubMed, Web of Science, Scopus, and PEDro databases were searched for randomized clinical trials assessing the effect of tDCS on gait in patients with PD. Results Eighteen studies were included in this systematic review. Overall, tDCS targeting the motor cortex and supplementary motor area bilaterally seems to be promising for gait rehabilitation in PD. Studies of tDCS targeting the dorosolateral prefrontal cortex or cerebellum showed more heterogeneous results. More studies are needed to systematically compare the efficacy of different tDCS protocols, including protocols applying tDCS alone and/or in combination with conventional gait rehabilitation treatment in PD. Conclusions tDCS is a promising intervention approach to improving gait in PD. Anodal tDCS over the motor areas has shown a positive effect on gait, but stimulation of other areas is less promising. However, the heterogeneities of methods and results have made it difficult to draw firm conclusions. Therefore, systematic explorations of tDCS protocols are required to optimize the efficacy.

scholarly journals Therapeutic Effects of Hydrogen in Animal Models of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kyota Fujita ◽  
Yusaku Nakabeppu ◽  
Mami Noda
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Animal Studies ◽  
Clinical Symptoms ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Cellular Apoptosis ◽  
6 Hydroxydopamine

Since the first description of Parkinson's disease (PD) nearly two centuries ago, a number of studies have revealed the clinical symptoms, pathology, and therapeutic approaches to overcome this intractable neurodegenerative disease. 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are neurotoxins which produce Parkinsonian pathology. From the animal studies using these neurotoxins, it has become well established that oxidative stress is a primary cause of, and essential for, cellular apoptosis in dopaminergic neurons. Here, we describe the mechanism whereby oxidative stress evokes irreversible cell death, and propose a novel therapeutic strategy for PD using molecular hydrogen. Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.

scholarly journals Potential Role of Caffeine in the Treatment of Parkinson’s Disease

2016 ◽  
Vol 10 (1) ◽  
pp. 42-58 ◽  
Author(s):  
Mohsin H.K. Roshan ◽  
Amos Tambo ◽  
Nikolai P. Pace
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Clinical Trials ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Muscle Rigidity ◽  
Therapeutic Effects ◽  
Motor Symptoms ◽  
Wide Range

Parkinson’s disease [PD] is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of α-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from bothin vivoandin vitrostudies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2Areceptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials.

scholarly journals Resveratrol in Rodent Models of Parkinson’s Disease: A Systematic Review of Experimental Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Cheng-Fu Su ◽  
Li Jiang ◽  
Xiao-Wen Zhang ◽  
Ashok Iyaswamy ◽  
Min Li
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Motor Function ◽  
Quantitative Methods ◽  
Experimental Studies ◽  
Future Research ◽  
Rodent Models ◽  
Neuroprotective Effects ◽  
Systematic Analysis

Parkinson’s disease (PD) is a common neurodegenerative disease featured by progressive degeneration of nigrostriatal dopaminergic neurons (DA) accompanied with motor function impairment. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-PD efficacy in PD models. Among those compounds, resveratrol, a polyphenol found in many common plants and fruits, is more effective against PD. Resveratrol has displayed a potent neuroprotective efficacy in several PD animal models. However, there is still no systematic analysis of the quality of methodological design of these studies, nor of their results. In this review, we retrieved and analyzed 18 studies describing the therapeutic effect of resveratrol on PD animal models. There are 5 main kinds of PD rodent models involved in the 18 articles, including chemical-induced (MPTP, rotenone, 6-OHDA, paraquat, and maneb) and transgenic PD models. The neuroprotective mechanisms of resveratrol were mainly concentrated on the antioxidation, anti-inflammation, ameliorating mitochondrial dysfunction, and motor function. We discussed the disadvantages of different PD animal models, and we used meta-analysis approach to evaluate the results of the selected studies and used SYRCLE’s risk of bias tool to evaluate the methodological quality. Our analytical approach minimized the bias of different studies. We have also summarized the pharmacological mechanisms of resveratrol on PD models as reported by the researchers. The results of this study support the notion that resveratrol has significant neuroprotective effects on different PD models quantified using qualitative and quantitative methods. The collective information in our review can guide researchers to further plan their future experiments without any hassle regarding preclinical and clinical studies. In addition, this collective assessment of animal studies can provide a qualitative analysis of different PD animal models, either to guide further testing of these models or to avoid unnecessary duplication in their future research.

scholarly journals The Role of Architecture and Design in the Management of Parkinson’s Disease: A Systematic Review

2020 ◽  
Vol 10 (4) ◽  
pp. 1301-1314
Author(s):  
Joana Beisl Ramos ◽  
Gonçalo S. Duarte ◽  
Raquel Bouça-Machado ◽  
Margherita Fabbri ◽  
Tiago A. Mestre ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Fear Of Falling ◽  
Experimental Studies ◽  
Postural Instability ◽  
Functional Mobility ◽  
Housing Type ◽  
Architecture And Design ◽  
The Impact

Background: Parkinson’s disease (PD) is a neurological condition characterized by the development of daily disabling symptoms. Although the architecture and design of a PD patient’s environment can hinder or facilitate full participation in daily activities, their putative role in the management of these patients has received little attention to date. Objective: We conducted a systematic review to evaluate the evidence of architectural and design features in the management of people with PD. Methods: An electronic database search of observational and experimental studies was conducted in MEDLINE and Embase from inception to May 2020, with two independent reviewers identifying the studies. Falls, fear of falling, postural instability, gait impairment/disability, and functional mobility were our outcomes of interest. Results: Thirty-six studies were included, among which nineteen were observational and seventeen were experimental studies (overall participants = 2,965). Pavement characteristics, notably unstable surfaces and level differences, were found to be a major cause of falling. Ground-based obstacles and confined/narrowed spaces were found to disturb gait, increase postural instability, and decrease functional mobility. Housing type did not appear to increase risk of falling, nor to significantly explain concerns about falling. Conclusion: Findings suggest a need to adjust architectural features of the surrounding space to ensure appropriate care and provide a safe environment to PD patients. More evidence about the impact of such modifications on PD outcomes is needed.

scholarly journals Acupuncture-Related Therapies for Parkinson's Disease: A Meta-Analysis and Qualitative Review

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiaopeng Wen ◽  
Kunbin Li ◽  
Hao Wen ◽  
Qian Wang ◽  
Zhiyuan Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Hamilton Depression Scale ◽  
High Quality ◽  
Conventional Medication

Objective: This systematic review and meta-analysis aimed to assess the effects of the combination of acupuncture-related therapies with conventional medication compared with conventional medication in patients with Parkinson's disease (PD).Methods: A literature search within eight databases [including Medline, Embase, the Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang Database] was performed covering a time frame from their inception to August 2020. Randomized controlled trials (RCTs) comparing acupuncture-related therapies combined with conventional medication vs. conventional medication in patients with PD were eligible. Two authors independently assessed the risk of bias. Assessments were performed with the total and subscales scores of the Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), the dosage of Madopar, Mini-Mental State Examination (MMSE), and 17-item Hamilton Depression Scale (HAMD). Data were analyzed by adopting the Cochrane Collaboration's RevMan 5.4 (Review Man, Copenhagen, Denmark); and mean effect sizes and 95% confidence intervals were estimated. Tests for heterogeneity were used to assess differences in treatment effects across different types of acupuncture used.Results: Sixty-six trials met the inclusion criteria, of which 61 trials provided data for the meta-analysis. We defined high-quality articles as those with a low risk of bias in four or more domains; and only 10 (15.15%) articles were of high quality. Compared with the controls, acupuncture-related therapies with conventional medication achieved a benefit in the primary outcomes of UPDRS (motor subscore: −3.90, −4.33 to −3.49, P &lt; 0.01; total score: −7.37 points, −8.91 to −5.82, P &lt; 0.001; activities of daily living subscore: −3.96, −4.96 to −2.95, P &lt; 0.01). For the subgroup difference test among the effects of different acupuncture methods, significant differences existed in outcomes with the UPDRS-III, UPDRS-I, UPDRS-IV, and PDQ-39 scores and Madopar dosage, while non-significant differences existed with the UPDRS-total, UPDRS-II, HAMD, and MMSE scores.Conclusions: Acupuncture-related therapies combined with conventional medication may benefit individuals with PD. Our review findings should be considered with caution because of the methodological weaknesses in the included trials. Future, large randomized trials of acupuncture-related therapies for PD with high methodological quality are warranted.Systematic Review Registration: Identifier CRD42021228110.

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