Parkinson Disease
Conditions
Brief summary
Levodopa-induced dyskinesia severely limits the use of levodopa in Parkinson's disease and constitutes a debilitating complication of dopaminergic treatment in late stage. Among several neurobiological mechanisms identified so far, the investigators have established in experimental models the key role of D1 receptor hypersensitivity and aRas-ERK signalling pathway. As the very same dopamine receptor machinery and the Ras-ERK pathway are present in blood lymphocytes, the investigators wish to test the hypothesis that the level of ERK phosphorylation in lymphocytes is a biomarker of levodopa-induced dyskinesia in Parkinson's Disease. The study will be performed in dyskinetic levodopa-treated patients and non-Parkinson's Disease controls. Blood sampling off and on levodopa treatment (1 hour post-dose), as well as clinical data collection will be done during a scheduled pre-op work-up (deep brain stimulation). Subsequently, suspended lymphocytes from blood samples will be immunolabelled using an anti-pERK antibody and mean fluorescence intensity and percent of labelled lymphocytes will be assessed by flow cytometry. Additionally, plasma and urine samples will be collected on et off for dosage of dopamine. The motor effect of levodopa will be assessed through UPRSIII rating scale and eye movement (saccades) speed by non-invasive oculometric recordings.
Interventions
OTHERClinical variables
Demography, disease duration, treatment duration, current treatment, daily intake of levodopa, Disease stage (Hoehn and Yahr, HY), motor score (UPDRS III) and dyskinesia severity (UPDRS IV). Biological variables.
Sponsors
Université Victor Segalen Bordeaux 2
University Hospital, Bordeaux
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Consecutive eligible PD in- and outpatients selected at the university hospital of Bordeaux. * Non-demented patients (DSM IV) who are able to give their informed consent and who are affiliated to the social security. * Controls: Subjects without known neurological disorder, non-demented, able to give their informed consent and affiliated to the social security.
Exclusion criteria
* Patients: Atypical or secondary parkinson disease. * Previous or current cancer or malignant haemopathy. * Known auto-immune disease. * Anti-neoplastic or immuno-modulator treatment (particularly corticosteroids). Immuno-deficient subjects. * Acute viral infection (within 2 weeks after resolving). Statin drug intake. Demented subject (DSMIV). * Controls: Same criteria as above plus any neurological disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ERK phosphorylation | Day 1 | Distribution of variables and difference in the state of ERK phosphorylation in two contrasted groups : the dyskinetic levodopa-treated PD group and control group. |
Secondary
| Measure | Time frame |
|---|---|
| plasma and urinary dopamine in on and off state | Day 1 |
| measure derivatives of morphine | Day 1 |
Countries
France
Outcome results
None listed