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The Michael J. Fox Foundation Leads Charge to Develop Alpha-Synuclein PET Tracer to Image Parkinson's Disease Biomarker
Date:11/7/2013

ns and that can bind to alpha-synuclein. With this tool, they could visualize the distribution of alpha-synuclein in the brain. Such tracking of these aggregates would help diagnose and track disease progression and monitor therapies targeted at reducing alpha-synuclein levels. As drugs targeting Lewy bodies move through development, researchers could test whether they change levels of alpha-synuclein rather than rely on a change in clinical symptoms, as they do now.

Development of a tracer of the protein beta-amyloid transformed Alzheimer's disease research, leading to insights on how that pathology leads to cognitive decline. PD researchers hope the ability to image alpha-synuclein could allow similar breakthroughs in not only Parkinson's disease, but also related parkinsonisms such as Lewy body dementia, multiple system atrophy and progressive supranuclear palsy.

In 2011 MJFF assembled a consortium with a contract research organization and two academic groups to collaborate on the pursuit of an alpha-synuclein tracer. To identify molecules that bind selectively and with high affinity for the protein, researchers screened 100,000 compounds selected through computational chemistry based on the alpha-synuclein structure. They have identified several promising compounds and continue to optimize them and radiolabel the most promising for further development.

"It is unfortunately a process of trial-and-error. While we're closing in on the compounds with the greatest likelihood of success, there are still hurdles to cross in the next phase of development," said Chester Mathis, Ph.D., director of the PET Facility at the University of Pittsburgh and a member of the MJFF Alpha-Synuclein Imaging Consortium.

The challenges this Parkinson's tracer faces are plenty. Alpha-synuclein is not very abundant in the brain, so the binding compound must be highly selective. Also, it accumulates intracellularly, so in addition to
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SOURCE The Michael J. Fox Foundation for Parkinson's Research
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