Identification of a Biomarker Predictive of Evolution of Parkinson Disease

Brain Microglial Activation in the Early Stage of the Parkinson's Disease: a Predictive Biomarker of the Evolution?

Phase II, Open-labeled, Prospective, Multi-center study of assessing the link between microglial activation and dopaminergic denervation kinetics in the early stage of Parkinson disease, by using the imaging of [18F]DPA-714 a new ligand of Translocator Protein-18 kDa (TSPO) by Positron Emission Tomography (PET).

The Parkinson's disease ( MP) is a frequent but heterogeneous neurodegenerative disease in term of clinical presentation(display) and evolutionary profile. The therapeutic coverage(care) of the patients would thus be personalized Such an approach remains still in its infancy in 2017. Better know the factors which determine the evolutionary clinical subcategories is a major question of the current researches on the Parkinson disease. Nigrostriaial inflammation is an interesting candidate. Microglia activation is closely associated with the degenerative process.

Development of the molecular imaging allows to study nigrostriatal inflammation in vivo in human by positron emission tomography (PET) by using the radiotracer of the protein of translocation of 18KDa ( TSPO), considered as a marker of microglia activation Some studies showed an increase of the inflammation in the striatum and in the substantia nigra, the sites of the dopaminergic degeneration (The lesional core of the Parkinson disease is the damage of the dopaminergic nigrostriatale way). However data remain rare and concern small number of patients. Some data are inconsistent because of problems of specificity of the ligands used and variation between populations of studied patients (duration of disease evolution).

In this study, investigators suggest studying by imaging TEP using a ligand new of the TSPO, [18F]DPA-714, microglial brain activation in the early stage of the Parkinson disease and determine wether it is predictive of speed of disease progression.

Inclusion Criteria:

• Patients having a Parkinson's disease diagnosed according to the criteria UKPDSBB.
• Diagnosis done less than three years before the date the inclusion.
• Patient Age at diagnosis : between 40 and 65 years.
• Absence of clinical arguments for an associated neurovascular pathology.
• Written consent obtained.
• HAB polymorphism in the genotyping of TSPO gene.
• Brain MRI without following abnormalities: cortical or sub-cortical atrophy or hippocampal atrophy (Scheltens score ≥2), vascular encephalopathy (Fazekas score > 2, > 10 microbleed) or showing signs in favour of atypical parkinson syndrome.

Exclusion Criteria:

• Pregnant woman
• Minor
• Adult protected by the law
• Contraindication to PET-scan
• Contraindication to brain MRI
• History of inflammatory or dysimmune chronic disease
• History of psychiatric disease or drug addiction
• History of cognitive disorders (MMS<26)
• Hypersensibility to iodine derivates or one of these components
• Long-term Treatments which can interfere in neuroinflammation process
• Treatments / substances susceptible to interfere with the 18F-DPA-714
• TSPO gene Polymorphisms rs6971 corresponding to groups of affinity of low affinity (LAB=Low Affinity Binder) or moderated MAB = Mixed Affinity Binder)
• Modification of diagnosis of Parkinson disease during follow-up, in particular towards an atypical parkinson-like syndrome