Cores

Administrative Core

Core Lead: Robert H. Mach PhD

The Administrative Core coordinates all activities associated with the CW2IP2. This includes monitoring the progress of the cores and projects through biweekly calls of the Center Executive Steering Committee and joint calls with the members of the Clinical Core, and organization of the bi-annual conference call and annual meeting of the External Liaison Committee. The Administrative Core also provides the oversight needed to direct the efficient operation of the CW2IP on a day-to-day basis, such as the shipment of research materials between the different labs involved in the consortium and financial oversight.

 

Given the multi-site structure of the Medicinal Chemistry and Radiochemistry (MCRC) Core, a key component of the Administrative Core is the Center Executive Steering Committee, which consists of the site PIs of the MCRC core. The Executive Steering Committee is responsible for identifying which compounds identified as hits will be chosen for full evaluation in structure-activity relationship studies. The Administrative Core is also responsible for the obtaining regulatory approval for the PET radiotracers chosen for translation for first-in-human studies.

 

Medicinal Chemistry and Radiochemistry Core

Core Leads: Robert H. Mach PhD, Zhude Tu PhD, E. James Petersson PhD, Chester A. Mathis PhD, Neil Vasdev, PhD

The Medicinal Chemistry and Radiochemistry (MCRC) Core represents the central hub of activity of this U19 Center. The initial focus of the MCRC Core is the use of novel in silico methods for the identification of lead compounds for PET radiotracer development for alpha synuclein (Asyn) and 4R tau, a new approach to lead compound identification in the field of PET radiotracer development. Once in silico hits have been confirmed as true lead compounds from the radioligand binding studies conducted in Projects 1 and 2, the MCRC Core will be responsible for conducting structure-activity relationship (SAR) studies to identify compounds with the appropriate properties for radiolabeling and additional in vitro and in vivo characterization. The radiolabeling studies will be conducted by the radiochemistry component of the MCRC Core. This Core will also conduct scale-up synthesis of precursors and standards required for the imaging studies conducted by the Clinical Imaging Core.  

 

Clinical Core

Core Lead: Joel Perlmutter MD

This Clinical Core will implement first in human PET imaging with new radiotracers targeting α-synuclein (α-syn) and 4 repeat tau (4R tau). Radiotracers will be developed preclinically in the Med Chem Core and in Projects 1 and 2 focusing on α-syn and 4R tau, respectively. The Clinical Core will focus α-syn radiotracers on two synucleinopathies, Parkinson disease (PD) and Multiple Systems Atrophy (MSA), and focus 4R tau radiotracers on two different tauopathies, progressive supranuclear palsy (PSP) and familial frontotemporal dementias (FTD) due to mutation in Microtubule Associated Protein Tau (MAPT) gene. Participants will be drawn from multiple ongoing clinical cohorts of FTD, PSP, PD and MSA.

 

Clinical Core functions include interaction with the Executive Steering Committee to determine when to start human studies, coordinate required regulatory activities for radiotracer candidates, carry out early safety assessments including whole body dosimetry studies at Penn; coordinate patient selection criteria, centrally collect and serve all imaging and demographic data, coordinate tracer kinetic methods development and validation for human imaging, and coordinate all data to efficiently enable GO-NOGO decisions for candidate radiotracers.