scholarly journals A Systematic Review of Parkinson’s Disease Pharmacogenomics: Is There Time for Translation into the Clinics?

2021 ◽  
Vol 22 (13) ◽  
pp. 7213
Author(s):  
Vladimira Vuletić ◽  
Valentino Rački ◽  
Eliša Papić ◽  
Borut Peterlin
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Methylenetetrahydrofolate Reductase ◽  
Treatment Options ◽  
Current Evidence ◽  
Clinical Implementation ◽  
Public Health Burden ◽  
Manual Search

Background: Parkinson’s disease (PD) is the second most frequent neurodegenerative disease, which creates a significant public health burden. There is a challenge for the optimization of therapies since patients not only respond differently to current treatment options but also develop different side effects to the treatment. Genetic variability in the human genome can serve as a biomarker for the metabolism, availability of drugs and stratification of patients for suitable therapies. The goal of this systematic review is to assess the current evidence for the clinical translation of pharmacogenomics in the personalization of treatment for Parkinson’s disease. Methods: We performed a systematic search of Medline database for publications covering the topic of pharmacogenomics and genotype specific mutations in Parkinson’s disease treatment, along with a manual search, and finally included a total of 116 publications in the review. Results: We analyzed 75 studies and 41 reviews published up to December of 2020. Most research is focused on levodopa pharmacogenomic properties and catechol-O-methyltransferase (COMT) enzymatic pathway polymorphisms, which have potential for clinical implementation due to changes in treatment response and side-effects. Likewise, there is some consistent evidence in the heritability of impulse control disorder via Opioid Receptor Kappa 1 (OPRK1), 5-Hydroxytryptamine Receptor 2A (HTR2a) and Dopa decarboxylase (DDC) genotypes, and hyperhomocysteinemia via the Methylenetetrahydrofolate reductase (MTHFR) gene. On the other hand, many available studies vary in design and methodology and lack in sample size, leading to inconsistent findings. Conclusions: This systematic review demonstrated that the evidence for implementation of pharmacogenomics in clinical practice is still lacking and that further research needs to be done to enable a more personalized approach to therapy for each patient.

Brain Neuroimaging of Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease: A Systematic Review

2021 ◽  
pp. 1-15
Author(s):  
Rafail Matzaras ◽  
Kuangyu Shi ◽  
Artemios Artemiadis ◽  
Panagiotis Zis ◽  
Georgios Hadjigeorgiou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Manifestations ◽  
Brain Regions ◽  
Primary Objective ◽  
Current Evidence ◽  
Nuclear Medicine Imaging ◽  
Sleep Behavior ◽  
Imaging Results

Background: REM-sleep behaviour disorder (RBD) is a parasomnia and a common comorbidity in Parkinson’s disease (PD). There is evidence that the presence of RBD is associated with more severe PD. The differences in the clinical manifestations and the natural history are likely to imply underlying differences in the pathophysiology among PD patients with and without RBD. The increasing number of neuroimaging studies support this notion. Objective: Our primary objective was to review the current evidence regarding the brain neuroimaging findings in PD patients with RBD (PDRBD). Methods: A systematic review of articles, published in PubMed between January 1, 2000 and September 23, 2020 was performed. We evaluate previous studies that assessed PD patients with RBD using various brain structural and functional magnetic resonance imaging (MRI) techniques and brain nuclear medicine imaging. Results: Twenty-nine studies, involving a total of 3,347 PD subjects among which 912 subjects with PDRBD, met the selection criteria and were included. The presence of RBD in PD patients is associated with structural and functional alterations in several brain regions, mainly in brainstem, limbic structures, frontotemporal cortex, and basal ganglia, raising the hypothesis of a PDRBD neuroimaging phenotype. Conclusion: The current review provides up-to-date knowledge in this field and summarizes the neurobiological/neuroimaging substrate of RBD in PD.

Levodopa Therapy for Parkinson's Disease: History, Current Status and Perspectives

2020 ◽  
Vol 19 (8) ◽  
pp. 572-583
Author(s):  
Helle Bogetofte ◽  
Arezo Alamyar ◽  
Morten Blaabjerg ◽  
Morten Meyer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Substantia Nigra Pars Compacta ◽  
Current Status ◽  
Current Evidence ◽  
Muscle Rigidity

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by a preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta. This results in a profound decrease of striatal dopamine (DA) levels, which in turn leads to the cardinal motor symptoms of PD; muscle rigidity, hypo- and bradykinesia and resting tremor. Even 50 years after its initial use, the DA precursor levodopa (L-dopa), is still the most effective medical therapy for the symptomatic treatment of PD. Long-term L-dopa treatment is however, unfortunately associated with undesirable side effects such as motor fluctuations and dyskinesias. Furthermore, despite the disease alleviating effects of L-dopa, it is still discussed whether L-dopa has a neurotoxic or neuroprotective effect on dopaminergic neurons. Here we review the history of L-dopa, including its discovery, development and current use in the treatment of PD. We furthermore review current evidence of the L-dopa-induced side effects and perspectives of L-dopa treatment in PD compared to other established treatments such as DA-agonists and the inhibitors of catechol-o-methyltransferase and monoamine oxidase B.

Safety and Efficacy of Levetiracetam for the Management of Levodopa- Induced Dyskinesia in Patients with Parkinson’s Disease: A Systematic Review

2019 ◽  
Vol 18 (4) ◽  
pp. 317-325 ◽  
Author(s):  
Mahmoud A. Ebada ◽  
Souad Alkanj ◽  
Mohamed Ebada ◽  
Ahmed H. Abdelkarim ◽  
Ahmed Diab ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Involuntary Movement ◽  
Current Evidence ◽  
Open Label ◽  
Small Effect Size ◽  
Prisma Statement ◽  
Poor Tolerability

Background: Levetiracetam, a novel antiepileptic drug, has shown antidyskinetic effects in experimental animal models of Parkinson's disease (PD). The tolerability and efficacy of levetiracetam in reducing the levodopa-induced dyskinesia (LID) in PD patients have not been established. Therefore, this study aims to synthesize evidence from published prospective clinical trials about the efficacy of levetiracetam for the management of LID in PD patients. Methods: We followed the PRISMA statement guidelines during the preparation of this systematic review. A computer literature search of PubMed, EBSCO, Scopus, MEDLINE, and the web of science was carried out. We selected prospective clinical trials assessing the anti-dyskinetic efficacy of levetiracetam for treating LID in patients with PD. The Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression Score (GCI), UPDRS III, and UPDRS IV were considered as the primary outcome measures; their data were extracted and reviewed. Results: Our review included seven clinical trials with a total of 150 patients. Of them, three studies were randomized controlled trials, and the remaining were open-label single arm trials. Four studies reported poor tolerability of the levetiracetam with mild anti-dyskinetic effects. Levetiracetam slightly improved the UPDRS-IV and AIMS scores with small effect size. In the remaining three studies, levetiracetam failed to exhibit any anti-dyskinetic effects. Conclusion: Current evidence does not support the efficacy of the levetiracetam for treating LID in PD patients, however, due to the limited number of published randomized control trials (RCTs), further RCTs are required.

scholarly journals Effects of Nordic walking on Parkinson’s disease: a systematic review of randomized clinical trials

2016 ◽  
Vol 23 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Franciele Cascaes da Silva ◽  
Rodrigo da Rosa Iop ◽  
Beatriz Angélica Valdivia Arancibia ◽  
Elizandra Gonçalves Ferreira ◽  
Salma Stéphany Soleman Hernandez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Disease Stage ◽  
Control Group ◽  
Nordic Walking ◽  
Positive Effects ◽  
Manual Search

ABSTRACT Several exercise modalities improve the symptoms of Parkinson’s Disease (PD). Among the variety of physical exercises, Nordic walking has been used. The aim of this study was to summarize scientific literature on effects of Nordic walking on patients with PD by a systematic review of randomized clinical trials. The following electronic databases were selected: MEDLINE by Pubmed, Cochrane, PEDro, SCOPUS and Web of Science and articles identified by manual search, without restriction of date and language. The reviewers evaluated the articles and selected studies according to the eligibility criteria. The following data were extracted from the selected studies: publication identification, participants’ characteristics (sex, age, disease stage, duration of disease), experimental intervention characteristics, control group characteristics, duration, follow-up time, outcome measures and main results. Nordic walking programs with moderate and high intensities, with a minimum of 12 sessions of 60 minutes in a period from 6 to 24 weeks promoted positive effects on the severity, gait, balance, quality of life, functional capacity and motor function in patients with PD.

Rapid Diagnosis of Parkinson’s Disease from Sebum using Paper Spray Ionisation Ion Mobility Mass Spectrometry

2020 ◽  
Author(s):  
Depanjan Sarkar ◽  
Drupad Trivedi ◽  
Eleanor Sinclair ◽  
Sze Hway Lim ◽  
Caitlin Walton-Doyle ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ion Mobility ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
Ion Mobility Mass Spectrometry ◽  
Paper Spray ◽  
Molecular Features ◽  
Validation Set

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

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