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Pet Imaging to Determine Regional and Temporal Trajectories of Reactive Astrocytosis in Parkinson’s Disease

Study Rationale: Neuroinflammation is a known process accompanying Parkinson’s disease (PD) neuropathology. During this process, specific brain cell populations become chronically activated, including a cell population called astrocytes. First studies show early involvement of these cells in PD pathology with differences in activity levels and brain distribution between various PD disease stages. While more and more therapeutic strategies are emerging for PD, including disease modifying therapies addressing neuroinflammation, biomarkers for prediction of disease progression and objective read out parameters for interventional trials are still missing.

Hypothesis: It is hypothesized that neuroinflammation is a dynamic process in PD and might be a suitable target for the development of new PD biomarkers.

Study Design: This study will use [18F]D2-Deprenyl-PET – a technique for imaging and quantifying astrocyte activity levels in patients’ brains, blood and cerebrospinal fluid measures of these patients for Glial fibrillary acidic protein (GFAP) – a structure protein of astrocytes. We will assess both biomarkers as surrogates of astrocyte activity levels in patients with early-stage PD and advanced-stage PD at two time points with 12 months gap. For comparison, we will also assess patients with Multiple System Atrophy, a disease caused by the same protein as PD, and healthy controls using the same biomarkers.

Impact on Diagnosis/Treatment of Parkinson’s disease: With this project, we aim to better characterize neuroinflammatory changes in PD and establish new dynamic biomarkers targeting neuroinflammation. By measuring astrocytic activity with PET-based and fluid-based biomarkers, we aim to improve evaluation of disease severity and prediction of disease progression in different disease stages of PD and evaluate these new biomarkers as read out parameters for future interventional trials in PD.

Next Steps for Development: Depending on the results of this study, we will push [18F]D2-Deprenyl-PET imaging forward into a large multi-center efficacy trial of PD patients at various disease stages and try to establish this biomarker as a read-out parameters for future interventional trials.


Researchers

  • Matthias Brendel, MD, MHBA

    Munich Germany


  • Johannes Levin, MD

    Wendelsheim Germany


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