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Using Neurophysiology as a Stratification Tool for Synucleinopathy

Study Rationale: Although numerous disease-modifying drugs are being developed for Parkinson’s disease (PD), the current methods used to identify people suitable for clinical trials are costly, inaccessible and do not account for individuals’ differences in neurophysiology and disease progression. In this study, we will use two noninvasive, widely available and relatively inexpensive techniques —quantitative electroencephalography (qEEG) and transcranial magnetic stimulation (TMS) — to assess neurophysiological markers. Combining these techniques may help to reveal the connections between different brain regions that affect motor and cognitive functions, are uniquely sensitive to PD pathology and may account for differences in symptoms and rates of disease progression.

Hypothesis: The goal of this project is to identify surrogate markers that are sensitive to disease burden and disease progression in people with PD. We hypothesize that measurements collected with EEG and TMS will differ between individuals in the early stages of PD and healthy volunteers.

Study Design: In a two-year study conducted at UNIGE (Italy) and TASMC (Israel), we will recruit individuals with early PD (<5 years from diagnosis) who have either a genetic mutation associated with cognitive decline (GBA) or an idiopathic form of PD. The participants will undergo a neurological assessment, cognitive and motor evaluations and an electrophysiological examination with EEG and TMS. The EEG will include 20 minutes of resting-state measurements to quantify cortical brain activity. The TMS test will be paired with nerve stimulation to measure subcortical-cortical activity by means of Short and Long Afferent Inhibition (SAI / LAI).

Impact on Diagnosis/Treatment of Parkinson’s disease: A surrogate biomarker sensitive to disease severity and disease progression will provide an alternative to costly and invasive tests and can be used as a stratification tool for individuals with high disease burden and faster progression and as a direct measure of brain function with association to clinical outcome measures.

Next Steps for Development: Successful results will allow development of surrogate biomarkers for identifying individuals that are in the prodromal phase of PD, allowing them to enroll in disease-modifying clinical trials that offer the hope of slowing or stopping pathology at the earliest stages of the disease. 


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