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- Barker, Roger A., et al.
(författare)
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Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.
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| 2. |
- Griffiths, William J., et al.
(författare)
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The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
- 2021
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Disordered cholesterol metabolism is linked to neurodegeneration. In this study we investigated the profile of cholesterol metabolites found in the cerebrospinal fluid (CSF) of Parkinson’s disease (PD) patients. When adjustments were made for confounding variables of age and sex, 7α,(25R)26-dihydroxycholesterol and a second oxysterol 7α,x,y-trihydroxycholest-4-en-3-one (7α,x,y-triHCO), whose exact structure is unknown, were found to be significantly elevated in PD CSF. The likely location of the additional hydroxy groups on the second oxysterol are on the sterol side-chain. We found that CSF 7α-hydroxycholesterol levels correlated positively with depression in PD patients, while two presumptively identified cholestenoic acids correlated negatively with depression.
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| 3. |
- Roussakis, Andreas Antonios, et al.
(författare)
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Parkinson’s disease laterality : a 11C-PE2I PET imaging study
- 2020
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459.
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Tidskriftsartikel (refereegranskat)abstract
- Asymmetry of striatal dopaminergic deficits and motor symptoms is a typical characteristic of idiopathic Parkinson’s disease (PD). This study aims to characterise the trend of asymmetry in moderate-stage PD. We performed a 19-month longitudinal study in 27 patients with PET-CT imaging and appropriate clinical assessments. 11C-PE2I non-displaceable binding potential (BPND) was calculated bilaterally for the striatum at baseline and follow-up to estimate the in vivo density of striatal dopamine transporters (DAT). Changes in striatal 11C-PE2I BPND over time were more prominent in the ipsilateral as compared to contralateral side. Changes in MDS-UPDRS-III (motor component of the Movement Disorders Society Unified PD Rating Scale) were not different between the clinically most and least affected body sides. Our data support that the asymmetry in striatal dopaminergic degeneration becomes less prominent in moderate-stage PD. In contrast, during the above period, the asymmetry of motor symptoms was maintained between the clinically most and least affected body sides.
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| 4. |
- Williams-Gray, Caroline H, et al.
(författare)
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Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD)
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:7, s. 995-1003
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD.METHODS: Serum samples were collected in incident PD cases and age-matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C-reactive protein were measured, with data reduction using principal-component analysis, and relationships between component scores and motor (MDS Unified Parkinson's Disease Rating Scale - part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated.RESULTS: TNF-α, IL1-β, IL-2, and IL-10 were higher in PD (n = 230) than in controls (n = 93), P ≤ 0.001). Principal-component analysis of log-transformed data resulted in a 3-component solution explaining 51% of the variance. Higher "proinflammatory" and lower "anti-inflammatory" component scores were associated with more rapid motor progression over 36 months (P < 0.05), and higher "proinflammatory" component scores were associated with lower MMSE at all times (P < 0.05). Multiple linear regression analysis with adjustment for covariates confirmed "anti-inflammatory" component score was the strongest predictor of slower motor progression (β = -0.22, P = 0.002), whereas proinflammatory cytokines were associated with lower baseline MMSE (β = -0.175, P = 0.007).CONCLUSIONS: Serum immune marker profile is predictive of disease progression in PD and hence a potential prognostic biomarker. However, interventional trials are needed to clarify whether peripheral immune changes causally contribute to the progression of PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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