Antibody-based immunotherapies for Parkinsonian syndromes.
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ABSTRACT:
SUBMITTER: Tonges L
PROVIDER: S-EPMC6676879 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Antibody-based immunotherapies for Parkinsonian syndromes.
Tönges Lars L Zella Maria Angela Samis MAS
Neural regeneration research 20191101 11
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Project description:UnlabelledBackgroundMicroarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum antibody microarray to screen for differentially regulated cytokines in Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).ResultsSerum samples were obtained from patients with clinical diagnoses of PD (n = 117), MSA (n = 31) and PSP/CBS (n = 38) and 99 controls. Cytokine profiles of sera from patients and controls were analyzed with a semiquantitative human antibody array for 174 cytokines and the expression of 12 cytokines was found to be significantly altered. In a next step, results from the microarray experiment were individually validated by different immunoassays. Immunoassay validation confirmed a significant increase of median PDGF-BB levels in patients with PSP/CBS, MSA and PD and a decrease of median prolactin levels in PD. However, neither PDGF-BB nor prolactin were specific biomarkers to discriminate PSP/CBS, MSA, PD and controls.ConclusionsIn our unbiased cytokine array based screening approach and validation by a different immunoassay only two of 174 cytokines were significantly altered between patients and controls.
| S-EPMC3539904 | biostudies-literature
Project description:Atypical parkinsonism or atypical parkinsonian syndromes (APS) refer to a group of neurodegenerative disorders which mimic typical Parkinson's disease but poorly respond to levodopa treatment and deteriorate faster. APS are very rare and among them, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD) are the three relatively better characterized entities. The prevalence estimates of PSP, MSA, or CBD are mostly <10/105, and the incidence estimates are around 1/105 person-year; both estimates remain stable over the past few decades. The age at onset is relatively young for MSA at late 50s, followed by CBD at early 60s, and then PSP at late 60s. The gender difference is not significant in APS, although slight female predominance in CBD has been reported in literature. Little is known about genetic and environmental risk factors for PSP, MSA, and CBD; although the COQ2 mutation has been identified as a genetic risk for MSA, familial cases are extremely rare. Survival after symptom onset is generally within 10 years, but cases with longer disease duration do exist. Respiratory infection remains the major cause of death for APS, but cardiac arrest should be particularly considered in MSA. In addition to disease rarity, the phenotype-pathology discrepancy in APS makes the epidemiological studies even more challenging. Including biomarkers in future diagnostic criteria and establishing disease registry for collecting sufficient number of APS cases may increase the likelihood of finding modifiable risk factors for prevention and intervention.
| S-EPMC9020244 | biostudies-literature
Project description:Background/objectiveParkinson's disease (PD) and the atypical parkinsonian syndromes multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are movement disorders associated with degeneration of the central nervous system. Degeneration of the retina has not been systematically compared in these diseases.MethodsThis cross-sectional study used spectral-domain optical coherence tomography with manual segmentation to measure the peripapillar nerve fiber layer, the macular thickness, and the thickness of all retinal layers in foveal scans of 40 patients with PD, 19 with MSA, 10 with CBS, 15 with PSP, and 35 age- and sex-matched controls.ResultsThe mean paramacular thickness and volume were reduced in PSP while the mean RNFL did not differ significantly between groups. In PSP patients, the complex of retinal ganglion cell- and inner plexiform layer and the outer nuclear layer was reduced. In PD, the inner nuclear layer was thicker than in controls, MSA and PSP. Using the ratio between the outer nuclear layer and the outer plexiform layer with a cut-off at 3.1 and the additional constraint that the inner nuclear layer be under 46 µm, we were able to differentiate PSP from PD in our patient sample with a sensitivity of 96% and a specificity of 70%.ConclusionDifferent parkinsonian syndromes are associated with distinct changes in retinal morphology. These findings may serve to facilitate the differential diagnosis of parkinsonian syndromes and give insight into the degenerative processes of patients with atypical parkinsonian syndromes.
| S-EPMC3325949 | biostudies-literature
Project description:BackgroundBone health and fracture risk reduction are increasingly recognized as important issues in Parkinson's disease (PD). However, the evidence for fracture risk management in atypical parkinsonism (AP) is less clear. Guidance on management of bone health in PD has recently been published.ObjectivesTo evaluate the outcome of fracture risk assessment in a cohort of patients with AP, compared to a population with idiopathic PD.MethodsWe did a cross-sectional study of patients with PD or AP who had fracture risk assessed at two tertiary movement disorder centres. Data on fracture risk as assessed using QFracture and FRAX were collected. To assess for the effect of age on fracture risk we compared the risks of PD and AP patients aged ≤70 and >70 years.ResultsWe assessed 71 patients with AP and 267 with PD. Age, sex and body mass index were similar between groups; patients with AP were more likely to have fallen in the previous year. Major osteoporotic fracture risk was greater in patients with AP aged ≤70 compared to PD; no differences between groups were seen in those aged >70 years. 76% of those with AP, and 63% with PD, had an estimated fracture risk indicating bone-sparing treatment, but only 33% of patients with AP were receiving this where it was indicated.ConclusionThere is scope for considerable improvement in fracture risk assessment and treatment in atypical parkinsonism, taking into account the worse prognosis of this patient group.
| S-EPMC8015890 | biostudies-literature
Project description:The differential diagnosis of atypical parkinsonian syndromes is challenging. These severe and often rapidly progressive neurodegenerative disorders are clinically heterogeneous and show significant phenotypic overlap. Here, clinical, imaging, neuropathological and genetic features of multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration and frontotemporal lobar degeneration (FTLD) are reviewed. The terms corticobasal degeneration and FTLD refer to pathologically confirmed cases of corticobasal syndrome and frontotemporal dementia (FTD). Frontotemporal lobar degeneration clinically presents as the behavioral variant FTD, semantic variant primary progressive aphasia (PPA), non-fluent agrammatic variant PPA, logopenic variant PPA and FTD associated with motor neuron disease. While progressive supranuclear palsy and corticobasal syndrome have been called Parkinson-plus syndromes in the past, they are now classified as FTD-related disorders, reflecting that they pathologically differ from α-synucleinopathies like multiple system atrophy and Parkinson disease. The contribution of genetic factors to atypical parkinsonian syndromes is increasingly recognized. Genes involved in the etiology of FTLD include MAPT, GRN and C9orf72. Novel neuroimaging techniques, including tau positron emission tomography imaging, are being investigated. Multimodal magnetic resonance imaging approaches and automated magnetic resonance imaging volume segmentation techniques are being evaluated for optimized differential diagnosis. Current treatment options are symptomatic, and disease modifying therapies are under active investigation.
| S-EPMC7646945 | biostudies-literature
Project description:Coenzyme Q10 (CoQ10) has an important role as an antioxidant. Being that oxidative stress is one of the mechanisms involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases, several studies addressed the concentrations of CoQ10 in the different tissues of patients with PD and other parkinsonian syndromes (PS), trying to elucidate their value as a marker of these diseases. Other studies addressed the potential therapeutic role of CoQ10 in PD and PS. We underwent a systematic review and a meta-analysis of studies measuring tissue CoQ10 concentrations which shows that, compared with controls, PD patients have decreased CoQ10 levels in the cerebellar cortex, platelets, and lymphocytes, increased total and oxidized CoQ10 levels in the cerebrospinal fluid and a non-significant trend toward decreased serum/plasma CoQ10 levels. Patients with multiple system atrophy (MSA) showed decreased CoQ10 levels in the cerebellar cortex, serum/plasma, cerebrospinal fluid, and skin fibroblasts. Patients with Lewy body dementia (LBD) showed decreased cerebellar cortex CoQ10, and those with progressive supranuclear palsy (PSP) had decreased CoQ10 levels in the cerebrospinal fluid. A previous meta-analysis of studies addressing the therapeutic effects of CoQ10 in PD showed a lack of improvement in patients with early PD. Results of the treatment with CoQ10 in PSP should be considered preliminary. The potential role of CoQ10 therapy in the MSA and selected groups of PD patients deserves future studies.
| S-EPMC9225264 | biostudies-literature
Project description:Parkinsonism might precede, coincide, or follow the behavioral or language-predominant cognitive impairments characteristic of frontotemporal dementia (FTD). In this study, we analyze the hexanucleotide repeat expansions within C9orf72 gene in various parkinsonian syndromes because it is a recently identified important genetic cause of FTD. The expanded hexanucleotide repeat is only identified in our familial FTD patients but not in patients with predominant parkinsonism. The lack of association between abnormal C9orf72 repeat expansion and parkinsonian syndromes might imply pathogenic mechanisms other than tau or Lewy body pathology.
| S-EPMC4022748 | biostudies-literature
Project description:IntroductionNeuroinflammation has been established to be part of the neuropathological changes in Parkinson's disease (PD) and atypical parkinsonism (APD). Activated microglia play a key role in neuroinflammation by release of cytokines. Evidence of the disparity, if any, in the neuroinflammatory response between PD and APD is sparse. In this study, we investigated CSF cytokine profiles in patients with PD, multiple system atrophy (MSA), or progressive supranuclear palsy (PSP).MethodsOn a sensitive electrochemiluminescence-based platform (Quickplex, Meso Scale Discovery®), we examined a panel of C-reactive protein (CRP) and eight selected cytokines, IFN-γ, IL-10, IL-18, IL-1β, IL-4, IL-6, TGF-β1, and TNF-α, among patients with PD (n = 46), MSA (n = 35), and PSP (n = 39) or controls (n = 31). Additionally, CSF total tau protein levels were measured as a marker of nonspecific neurodegeneration for correlation estimates.ResultsCRP and the pro-inflammatory cytokines TNF-α, IL-1β, and Il-6 were statistically significantly elevated in MSA and PSP patients compared to PD patients but not compared to control patients. No analytes differed statistically significantly between MSA and PSP patients. The best diagnostic discrimination, evaluated by ROC curve (AUC 0.77, p = 007, 95% CI 0.660-0.867), between PD and MSA patients was seen for a subset of analytes: CRP, TNF-α, IL-1β, and IFN-γ.ConclusionAmong the investigated cytokines and CRP, we found a statistically significant increase of microglia-derived cytokines in MSA and PSP patients compared to PD patients.
| S-EPMC6215346 | biostudies-literature
Project description:Among people with Parkinson's disease (PD), non-motor symptoms (NMS) are a well-recognised cause of significant morbidity and poor quality of life. Yet, it is only more recently that NMS have been recognised to affect the lives of patients with atypical parkinsonian syndromes in a similar fashion. The aim of this article is to highlight and compare the relative prevalence of NMS among patients with atypical parkinsonian syndromes in the published literature, which largely remain underreported and unaddressed in routine clinical practice. All NMS that are recognised to occur in PD are also found to commonly occur in atypical parkinsonian syndromes. In particular, excessive daytime sleepiness is more prevalent among atypical parkinsonian syndromes (94.3%) compared to PD (33.9%) or normal controls (10.5%) (p < 0.001). Urinary dysfunction (not limited to urinary incontinence) is not only found to occur in MSA (79.7%) and PD (79.9%), but has also been reported in nearly half of the patients with PSP (49.3%), DLB (42%) and CBD (53.8%) (p < 0.001). Apathy is significantly more common among the atypical parkinsonian syndromes [PSP (56%), MSA (48%), DLB (44%), CBD (43%)] compared to PD (35%) (p = 0.029). Early recognition and addressing of NMS among atypical parkinsonian syndromes may help improve the holistic patient care provided and may encompass a range of conservative and pharmacotherapeutic treatments to address these symptoms.
| S-EPMC10421812 | biostudies-literature
Project description:Parkinson's disease (PD) and atypical Parkinsonian syndromes are progressive heterogeneous neurodegenerative diseases that share clinical characteristic of parkinsonism as a common feature, but are considered distinct clinicopathological disorders. Based on the predominant protein aggregates observed within the brain, these disorders are categorized as, (1) α-synucleinopathies, which include PD and other Lewy body spectrum disorders as well as multiple system atrophy, and (2) tauopathies, which comprise progressive supranuclear palsy and corticobasal degeneration. Although, great strides have been made in neurodegenerative disease research since the first medical description of PD in 1817 by James Parkinson, these disorders remain a major diagnostic and treatment challenge. A valid diagnosis at early disease stages is of paramount importance, as it can help accommodate differential prognostic and disease management approaches, enable the elucidation of reliable clinicopathological relationships ideally at prodromal stages, as well as facilitate the evaluation of novel therapeutics in clinical trials. However, the pursuit for early diagnosis in PD and atypical Parkinsonian syndromes is hindered by substantial clinical and pathological heterogeneity, which can influence disease presentation and progression. Therefore, reliable neuroimaging biomarkers are required in order to enhance diagnostic certainty and ensure more informed diagnostic decisions. In this article, an updated presentation of well-established and emerging neuroimaging biomarkers are reviewed from the following modalities: (1) structural magnetic resonance imaging (MRI), (2) diffusion-weighted and diffusion tensor MRI, (3) resting-state and task-based functional MRI, (4) proton magnetic resonance spectroscopy, (5) transcranial B-mode sonography for measuring substantia nigra and lentiform nucleus echogenicity, (6) single photon emission computed tomography for assessing the dopaminergic system and cerebral perfusion, and (7) positron emission tomography for quantifying nigrostriatal functions, glucose metabolism, amyloid, tau and α-synuclein molecular imaging, as well as neuroinflammation. Multiple biomarkers obtained from different neuroimaging modalities can provide distinct yet corroborative information on the underlying neurodegenerative processes. This integrative "multimodal approach" may prove superior to single modality-based methods. Indeed, owing to the international, multi-centered, collaborative research initiatives as well as refinements in neuroimaging technology that are currently underway, the upcoming decades will mark a pivotal and exciting era of further advancements in this field of neuroscience.
| S-EPMC7593544 | biostudies-literature