Phosphorylation of ERK1/2 in Patients With Parkinson's Disease

Study Overview
=================
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.

Official Title
-----------------
A Descriptive Study of Lymphocytic Phosphorylation of ERK1/2 in Patients With Parkinson's Disease With Dyskinesias and in Controls

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Other: Clinical variables
* Other: Clinical variables
* Other: Clinical variables


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Parkinson's Disease patient<br>levodopa-treated parkinson's disease (PD) patients | Other: Clinical variables<br>* 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.<br>Other: Clinical variables<br>* Eye movement recordings : non-invasive infra-red camera oculometry (EyeBrain) before and after (only parkinson's disease group) levodopa(10 to 15 minute/recording)<br>|
| Non Parkinson's disease controls<br>Non Parkinson's disease controls | Other: Clinical variables<br>* Demography, Biological variables.<br>Other: Clinical variables<br>* Eye movement recordings : non-invasive infra-red camera oculometry (EyeBrain) before and after (only parkinson's disease group) levodopa(10 to 15 minute/recording)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ERK phosphorylation | Distribution of variables and difference in the state of ERK phosphorylation in two contrasted groups : the dyskinetic levodopa-treated PD group and control group. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma and urinary dopamine in on and off state |  | Day 1 | 
| measure derivatives of morphine |  | Day 1 |