The main objective of this study is to develop a method to identify susceptible pathways of redox metabolism and bioenergetics in peripheral blood cells and induced pluripotent stem cells from patients with PD and DLB.
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main parameters of this study are the redox responses to pro-oxidant
challenge tests and bioenergetics functions such as mitochondrial respiration
and glycolytic activity. All patient groups will be characterized on
environmental exposures (smoking, insecticides, herbicides). For redox
susceptibility profiling, 20 ml blood will be drawn via venapuncture and a skin
biopsy will be performed. Differences in redox response to toxin challenge will
be determined in peripheral blood cells and induced pluripotent stem cells by
differential labelling of reduced and oxidized cysteines residues with
maleimide technology followed by Fluorescence Assisted Cell Sorting (FACS)
analysis.
Secondary outcome
Clinical assessments will be used to assess the progression of the core
features of PD, which is necessary to allocate patients to one of the
subgroups. The patients with DLB will be assessed clinically to be able to
compare the clinical function of PD and DLB patients.
Background summary
Different processes fundamental to neuronal vitality, including the maintenance
of protein homeostasis, oxidative stress and bioenergetics play a role in the
pathobiology of Parkinson*s disease (PD). Inter-individual differences in the
extent to which these processes are affected likely account for the existence
of differences in disease course and progression between PD patients. In this
study, we will focus on disturbances of redox metabolism and bioenergetics as a
potential pathobiological mechanism of PD and dementia with Lewy Bodies (DLB),
and their role in the expression of differences in progression between
patients.
Study objective
The main objective of this study is to develop a method to identify susceptible
pathways of redox metabolism and bioenergetics in peripheral blood cells and
induced pluripotent stem cells from patients with PD and DLB.
Study design
The proposed study will be a cross-sectional cohort and case-control study.
Study burden and risks
This study asks some effort from the patients and is not directly helping the
individual, but will provide more insight in the pathophysiology of PD and DLB.
The clinical assessments and venapunctures are routinely performed at our
outpatient clinic and are well tolerated by PD patients. If patients develop
fatigue, the assessment is adapted to the person*s wishes, or will be ended.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
For all participants a minimum age of 18 years is required.
All patients with Parkinson's Disease (PD) must fulfill the United Kingdom Parkinson's Disease Society Brain Bank criteria for idiopathic PD. Patients with Dementia with Lewy Bodies (DLB) must fulfill the McKeith DLB criteria and all patients must be diagnosed with PD or DLB by a movement disorder specialist.
All participants must be able to give informed consent.
Buffy coats of controls are included if they have no diseases of the central nervous system or conditions associated with the immune system.
Exclusion criteria
Participants should have no inflammatory diseases.
Participants are excluded when anti-inflammatory drugs (NSAIDs, corticosteroids), immunosuppressive medication or anti-oxidants (Vitamin C) are used.
Participants are excluded when having an infectious disease at the time of the measurements.
Participants who currently smoke are excluded.
Patients who underwent stereotactic surgery are excluded.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
Register | ID |
---|---|
CCMO | NL41867.058.12 |