Biomarkers of Parkinson disease are sorely needed for the assessment of disease status so that they may be used to design more efficient and informative clinical trials of disease-modifying therapies. Imaging would be ideal for PD and other chronic, neurodegenerative disorders as it is non-invasive, well-tolerated and available. However, current imaging techniques have not proved to be useful as sensitive or specific markers of PD disease expression. We plan to investigate whether the novel PET imaging probe, [18F]FDDNP can identify known, abnormal neuronal aggregates in subjects with Parkinson disease.
The pathologic hallmark of Parkinson disease is abnormal protein aggregates (Lewy bodies) in neurons. Lewy bodies are present in the brains of people with Parkinson disease and their distribution expands with disease duration. Our study will investigate the binding properties of the novel imaging probe, [18F]FDDNP, in an animal model of Parkinson disease and in human tissue to demonstrate that the underlying pathology can be identified with this marker. We will then use this probe for PET scans in living human subjects with early and later stages of Parkinson disease to determine whether abnormalities can be identified and if these abnormalities worsen in later stages of disease. We will also examine whether [18F]FDDNP binding correlates with abnormal brain metabolism (with an FDG-PET scan) and/or deficits in memory and cognition.
Currently, there is a wealth of basic research evidence being accumulated for the pathophysiologic basis of Parkinson disease that serves as a guide for the development of therapeutic strategies. However, there is a tight bottleneck that exists in the translation of this information into clinical treatment. One cause of this bottleneck is the lack of specific and reliable biomarkers of disease that serve to expedite clinical trials and identify agents that have the most promise as disease-modifying (or neuroprotective) therapies. This project seeks to determine whether [18F]FDDNP imaging can serve as a reliable biomarker of the underlying pathology in living human subjects with Parkinson disease. This will expedite the translation of potential neuroprotective agents into clinical treatment of persons with Parkinson disease
We are investigating the utility of the PET imaging molecule, amyloid ligand [18F] FDDNP, as a biomarker of pathology in PD. Our studies focus on differentiating location and intensity of ligand binding between subjects in early stages of PD when pathology is primarily confined to brainstem structures compared to subjects with later stages of PD when spread of Lewy body pathology to cortical structures is evident. Our work is ongoing and additional analyses will elucidate whether greater cortical [18F] FDDNP uptake is present in patients with a longer duration of disease. In addition, our studies of FDDNP binding in the alpha-synuclein overexpressing pre-clinical models are in progress.