Tracer to diagnose Parkinson’s via PET scans moving into clinical trial
$30M grant supports testing of radiotracer for toxic alpha-synuclein protein
A consortium dubbed Center Without Walls is planning to begin human testing of specific positron emission tomography (PET) radiotracers, which its scientists identified, to detect toxic proteins like alpha-synuclein, helping diagnose and monitor Parkinson’s and similar diseases.
Funded by a five-year, $30 million grant from the National Institutes of Neurological Disease and Stroke (NINDS), the consortium — led by the University of Pennsylvania’s medical school — will open clinical trials of two tracers for alpha-synuclein and one for 4-repeat tau, a marker of frontotemporal degeneration and progressive supranuclear palsy.
Researchers’ hope is that these imaging tools help to increase the number of neurological diseases that can be diagnosed with PET scans, as well as to monitor patients’ progression and response to treatments.
Potential for a faster diagnosis, better monitoring of patients
“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,” Robert Mach, PhD, a professor and director of radiochemistry research at the University of Pennsylvania, said in a university news release.
Parkinson’s is caused by the progressive dysfunction and death of dopaminergic neurons, nerve cells in the brain that are responsible for making dopamine. Dopamine is a brain chemical messenger important in motor control.
Although what exactly triggers the loss of these neurons is not fully known, the formation of clumps of misfolded alpha-synuclein protein is thought to play a key role.
PET scans use a radioactive drug, called a tracer, that is injected into the body and binds to specific proteins to make them visible and show areas of disease.
In recent years, PET scans have been able to image beta-amyloid plaques, markers of Alzheimer’s disease, thereby helping to diagnose and monitor Alzheimer’s progression. Developing more tracers with similar capacities is a research goal, but not an easy one.
“Due to the sheer number of possible molecules that could be used, the process of developing new radiotracers has been slow and complicated, like finding a needle in a haystack,” Mach said.
The project brings together scientists at the University of Pennsylvania and NINDS with those at The University of California San Francisco, the University of Pittsburgh, Washington University in St. Louis, and Yale University. The researchers are working to identify radiotracers to image alpha-synuclein in Parkinson’s and multiple system atrophy, and 4-repeat tau.
Over the consortium’s first five years, a team led by E. James Petersson, PhD, at the University of Pennsylvania developed a computational tool to evaluate millions of molecules and identify those worth testing. The tool then modeled how these molecules interacted with target proteins, determining those most likely to be effective. The alpha-synuclein and tau tracers were selected through this process.
It plans to open clinical trials into the selected tracers over the next five years, supported by the NINDS grant.
“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,” Mach said.
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