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 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.

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 Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

2018 ◽  
Vol 29 (3) ◽  
pp. 321-332 ◽  
Author(s):  
Suleiman Alhaji Muhammad ◽  
Norshariza Nordin ◽  
Sharida Fakurazi
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Conditioned Medium ◽  
Tissue Regeneration ◽  
Therapeutic Benefit ◽  
Risk Of Bias ◽  
Preclinical Studies

AbstractInjury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium inin vivoanimal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

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 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.

PTX3 secreted by human adipose-derived stem cells promotes dopaminergic neuron repair in Parkinson's disease via inhibiting apoptosis

2021 ◽  
Author(s):  
Changlin Lian ◽  
Qiongzhen Huang ◽  
Xiangyang Zhong ◽  
Zhenyan He ◽  
Boyang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Brain Slices ◽  
Human Mesenchymal Stem Cells ◽  
Substantia Nigra Pars Compacta ◽  
Therapeutic Effects ◽  
Label Free

Abstract Background Adipose-derived human mesenchymal stem cells (hADSCs) transplantation has recently emerged as a promising method in the treatment of Parkinson's disease (PD), however, the mechanism underlying has not been fully illustrated. Methods In this study, the therapeutic effects of the striatum stereotaxic injected hADSCs in 6-OHDA-induced mouse model were evaluated. Furthermore, an in vitro model of PD was constructed using tissue-organized brain slices. And the therapeutic effect was evaluated by co-culture of hADSCs and 6-OHDA-constructed brain slice. Within the analysis of hADSCs' exocrine proteins through RNA-seq, Human protein cytokine arrays and label-free quantitative proteomics, key extracellular factors were identified in hADSCs secretion environment.The degeneration of DA neurons and apoptosis were measured in PD samples in vivo and vitro models, and the beneficial effects were evaluated through quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot,Fluoro-Jade C, Tunel assay and immunofluorescence analysis. Results In this study, we discovered that hADSCs protected the dopaminergic (DA) neurons in vivo and vitro models.we identified Pentraxin3 (PTX3) as a key extracellular factor in hADSCs secretion environment. Moreover, we found that human recombinant Pentraxin3 (rhPTX3) treatment could rescue the physiological behaviour of the PD mice in-vivo, as well as prevent DA neurons from death and increase the neuronal terminals in the Ventral tegmental area (VTA) + substantia nigra pars compacta (SNc) and striatum (STR) on the PD brain slices in-vitro. Furthermore, within testing on the pro-apoptotic markers of PD mice brain following the treatment of rhPTX3, we found that rhPTX3 can prevent the apoptosis and the degeneration of DA neurons. Conclusions Overall, the current study investigated that PTX3, a hADSCs secreted protein, played a potential role in protecting the DA neurons from apoptosis and degeneration in PD progression as well as improving the motor performances in PD mice to give a possible mechanism of how hADSCs works in the cell replacement therapy in PD. Importantly, our study also provided potential translational implications for the development of PTX3-based therapeutics in PD.

scholarly journals Computerised cognitive training in Parkinson’s disease: a protocol for a systematic review and updated meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040656
Author(s):  
Hanna Malmberg Gavelin ◽  
Magdalena Domellöf ◽  
Isabella Leung ◽  
Anna Stigsdotter Neely ◽  
Carsten Finke ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Cognitive Training ◽  
Risk Of Bias ◽  
Effect Sizes ◽  
Motor Symptom ◽  
Intervention Design ◽  
Design Factors

IntroductionCognitive impairment is recognised as an important non-motor symptom in Parkinson’s disease (PD) and there is a need for evidence-based non-pharmacological interventions that may prevent or slow cognitive decline in this patient group. One such intervention is computerised cognitive training (CCT), which has shown efficacious for cognition across older adult populations. This systematic review aims to investigate the efficacy of CCT across cognitive, psychosocial and functional domains for people with PD and examine study and intervention design factors that could moderate CCT effects on cognition.Methods and analysisRandomised controlled trials investigating the effects of CCT in patients with PD without dementia, on cognitive, psychosocial or functional outcomes, will be included. The primary outcome is overall cognitive function. Secondary outcomes are domain-specific cognitive function, psychosocial functioning and functional abilities. We systematically searched MEDLINE, Embase and PsycINFO through 14 May 2020 to identify relevant literature. Risk of bias will be assessed using the revised Cochrane Risk of Bias tool. Effect sizes will be calculated as standardised mean difference of baseline to postintervention change (Hedges’ g) with 95% CI for each eligible outcome measure. Pooling of outcomes across studies will be conducted using random-effects models, accounting for dependency structure of effect sizes within studies. Heterogeneity will be assessed using τ2 and I2 statistic. Potential moderators, based on key study and intervention design factors, will be investigated using mixed-effects meta-regression models.Ethics and disseminationNo ethical approval is required. The findings will be disseminated in a peer-reviewed scientific journal.PROSPERO registration numberCRD42020185386.

scholarly journals A Multi-Scale Computational Model of Excitotoxic Loss of Dopaminergic Cells in Parkinson’s Disease

2020 ◽  
Author(s):  
Vignayanandam R. Muddapu ◽  
V. Srinivasa Chakravarthy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Computational Model ◽  
Neurodegenerative Disorder ◽  
Cell Loss ◽  
Therapeutic Interventions ◽  
Substantia Nigra Pars Compacta ◽  
Therapeutic Effects ◽  
Multi Scale

ABSTRACTParkinson’s disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc). Although the exact cause of the cell death is not clear, the hypothesis that metabolic deficiency is a key facor has been gaining attention in the recent years. In the present study, we investigate this hypothesis using a multi-scale computational model of the subsystem of the basal ganglia comprising Subthalamic Nucleus (STN), Globus Pallidus externa (GPe) and SNc. The model is a multiscale model in that interactions among the three nuclei are simulated using more abstract Izhikevich neuron models, while the molecular pathways involved in cell death of SNc neurons are simulated in terms of detailed chemical kinetics. Simulation results obtained from the proposed model showed that energy deficiencies occurring at cellular and network levels could precipitate the excitotoxic loss of SNc neurons in PD. At the subcellular level, the models show how calcium elevation leads to apoptosis of SNc neurons. The therapeutic effects of several neuroprotective interventions are also simulated in the model. From neuroprotective studies, it was clear that glutamate inhibition and apoptotic signal blocker therapies were able to halt the progression of SNc cell loss when compared to other therapeutic interventions, which only slows down the progression of SNc cell loss.

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