Funded Studies
Study Rationale: The ability to detect and monitor the accumulation of tau and alpha-synuclein aggregates in the brain is crucial to better understanding the pathophysiology of Progressive Supranuclear Palsy (PSP), Parkinson’s disease (PD) and related neurodegenerative disorders. Although markers have recently been developed to measure tau aggregation in Alzheimer’s Disease (AD), we currently lack positron emission tomography (PET) imaging agents selective for the form of tau found in PSP, 4R-tau, and for alpha-synuclein. Discovery of such markers would aid in diagnosis and allow the assessment of new therapies that target this class of neurodegenerative diseases.
Hypothesis: Our goal is to concurrently develop and validate selective PET imaging agents for PSP and PD.
Study Design: We will begin by carefully re-testing the imaging agents currently used to detect tau in AD for their potential 4R-sensitive tracers. At the same time, we will search for new chemical entities that are amenable for radiolabeling as PET probes for alpha-synuclein. Our team at MedChem Imaging, in collaboration with the Mathis group at the University of Pittsburgh, has been synthesizing and labeling the leading AD tau-PET tracers from other laboratories, and preparing new chemical entities as potential 4R-tau and alpha-synuclein PET probes. These compounds are being evaluated in brain tissues from different tau-based disorders and from people with PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: We are preparing a database of binding information and supplying radiolabeled precursors and reference standards to the Tau Consortium and our MJFF collaborators. We will then design and synthesize new chemical entities selective for 4R-tau or alpha-synuclein for future evaluation as PET imaging agents.
Next Steps for Development: Ultimately we will develop compounds that merit further preclinical and clinical evaluation as 4R-tau or alpha-synuclein PET imaging agents. These will enable evaluation of the effectiveness of new PSP and PD therapies and serve as “scaffolds” on which to base the design of additional selective PET imaging agents.