A Descriptive Study of Lymphocytic Phosphorylation of ERK1/2 in Patients With Parkinson's Disease With Dyskinesias and in Controls
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Parkinson Disease
- Sponsor
- University Hospital, Bordeaux
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- ERK phosphorylation
- Status
- Completed
- Last Updated
- 13 years ago
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 a"Ras-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.
Investigators
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.
Outcomes
Primary Outcomes
ERK phosphorylation
Time Frame: 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 Outcomes
- measure derivatives of morphine(Day 1)
- plasma and urinary dopamine in "on" and "off" state(Day 1)