Parkinson Disease Clinical Trial
Official title:
Molecular and Functional Imaging of Parkinson's Pathology in SNCA, Parkin and PINK1 Mutation Carriers
Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically
by bradykinesia, resting tremor, rigidity, and postural instability. The hallmark
pathophysiological alteration is a loss of dopaminergic transmission across the nigrostriatal
pathway. According to Braak's neuropathological staging of disease, the pathological process
in PD occurs in a gradual ascending fashion, starting from the olfactory bulb and progressing
to the brainstem, with preferential involvement of the raphe nuclei, which contain
serotonergic nuclei, and the noradrenergic locus coeruleus, before involving the substantia
nigra and thereafter the whole brain. Little is known about the mechanisms underlying
neuronal degeneration in PD and currently, no treatment is available to halt disease
progression in PD. The pathophysiological characterisation of phenomena occurring in the time
window between the pathological start of the disease and the onset of motor symptoms is
crucial to develop potential neuroprotective agents. Several genes causing, the so-called
monogenic parkinsonism, have been discovered providing important insights on the pathogenesis
of PD.
The objective of the study is to characterize the molecular phenomena underlying genetic
forms of parkinsonism and, therefore, providing further insights about the possible
mechanisms taking place in PD and help identify targets for disease-modifying therapeutics,
by using PET imaging with [11C]DASB (a marker of Serotonin transporter), SPECT imaging using
[123I]FP-CIT (a marker of the presynaptic Dopamine transporter), and multi-modal MRI imaging,
clinical markers (motor and non-motor symptoms and neuropsychological battery), blood and CSF
biomarkers.
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