A consortium led by the University of Pennsylvania is advancing the development of positron emission tomography (PET) radiotracers designed to detect toxic proteins, such as alpha-synuclein, associated with Parkinson's disease and related disorders. Supported by a five-year, $30 million grant from the National Institute of Neurological Disorders and Stroke (NINDS), the initiative aims to enhance the diagnosis and monitoring of these conditions through advanced imaging techniques.
The clinical trials will evaluate two tracers targeting alpha-synuclein and one for 4-repeat tau, a marker associated with frontotemporal degeneration and progressive supranuclear palsy. Researchers hope these tools will expand the range of neurological diseases diagnosable via PET scans and improve patient management.
Innovative Approach to Radiotracer Development
Robert Mach, PhD, a professor and director of radiochemistry research at the University of Pennsylvania, emphasized the collaborative nature of the project, stating, "The Center Without Walls combines clinical, scientific, imaging, and computational expertise from across institutions to develop a creative solution for this problem and has already resulted in clinical trials for three radiotracers that we identified."
Parkinson's disease is characterized by the progressive loss of dopaminergic neurons in the brain, leading to motor control impairment. While the exact cause remains elusive, the accumulation of misfolded alpha-synuclein protein is believed to play a critical role. PET scans, utilizing radioactive tracers that bind to specific proteins, offer a means to visualize these pathological markers.
Computational Tool Accelerates Tracer Discovery
E. James Petersson, PhD, at the University of Pennsylvania led a team that developed a computational tool to screen millions of molecules and identify promising radiotracer candidates. This tool models the interactions between molecules and target proteins, significantly accelerating the selection process. "Now that we’ve shown this computational chemistry model can identify the right molecules to bind to and trace [alpha-synuclein], our hope is that soon we can plug any protein target into the model and rapidly develop an effective radiotracer, and get these tracers into clinic sooner, so that we can better diagnose and manage a range of complicated diseases," said Mach.
The project unites researchers from multiple institutions, including the University of California San Francisco, the University of Pittsburgh, Washington University in St. Louis, and Yale University. Their collective efforts are focused on identifying radiotracers for imaging alpha-synuclein in Parkinson's disease and multiple system atrophy, as well as 4-repeat tau.
