$20M Grant Awarded for Research into Imaging Protein Misfolding in Parkinson’s

$20M Grant Awarded for Research into Imaging Protein Misfolding in Parkinson’s

The National Institute of Neurological Disorders and Stroke (NINDS) has awarded a five-year, $20 million grant to researchers looking for a way to image misfolded proteins in the brains of people with Parkinson’s and other neurodegenerative diseases, which could greatly advance diagnosis and disease monitoring.

Parkinson’s disease is thought to be a proteinopathy — a condition caused by proteins in the brain folding improperly, which sets off a chain reaction of misfolding in other proteins, eventually forming clumps and damaging the brain. Specifically, Parkinson’s is characterized by clumps of the protein alpha-synuclein.

Alzheimer’s disease is another proteinopathy, characterized by clumps of beta-amyloid. But there’s a crucial difference between the two in terms of how they are diagnosed and managed.

Brains can be imaged using a positron emission tomography (PET) scan, a technique in which a radioactive dye called a tracer is injected into the body. The tracer then binds to specific proteins, allowing clumps of these proteins to be visible on the scan. Although PET scans have been able to image beta-amyloid plaques for nearly a decade, the technology to visualize clumps of alpha-synuclein doesn’t yet exist.

The NINDS grant hopes to foster the development of a PET tracer that will bind to alpha-synuclein, as well as another tracer that will bind to 4R tau, a protein with important roles in frontotemporal degeneration and progressive supranuclear palsy.

This will be done using computers to find promising chemical formulations, then synthesizing and testing them. Although straightforward in theory, actually finding a molecule that can safely and specifically bind to these proteins is akin to finding a needle in a haystack, the researchers said. Hence, the importance of beginning with computer simulations.

“Finding a needle in a haystack is much easier when you have a machine made to find needles,” Andrew Siderowf, MD, a professor at the University of Pennsylvania and study leader, said in a press release.

The effort will also be led by researchers at Washington University-St. Louis, the University of Pittsburgh, the University of California-San Francisco, and Yale University.

Finding such a dye could allow screening for early detection of Parkinson’s disease before symptoms manifest. It could be used as an objective marker of an investigative treatment’s effectiveness in clinical trials.

“Currently, when testing new drugs for Parkinson’s, assessing the patient’s clinical symptoms is the only way to measure whether or not the treatment is working, but clinical features evolve very gradually,” Siderowf said. “Having an imaging biomarker that is sensitive to changes in a Parkinson’s pathology could greatly accelerate drug development.”

Robert H. Mach, PhD, a professor at the University of Pennsylvania and study co-investigator, summarized the researchers’ goal: “At the end of five years, we hope to have a radioactive tracer that will be able to detect Parkinson’s early on and provide detailed information about the disease’s progression, which is critical for discovering and testing new treatments.”

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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