Study Rationale:
In neurological disorders such as Parkinson’s disease (PD) or frontotemporal dementia, the proteins alpha-synuclein or tau are structurally altered and accumulate in clumps in the brain. These protein aggregates impair the function of nerve cells and cause neurodegeneration. They therefore serve as attractive targets for therapeutics and disease diagnosis. To enable these applications, a noninvasive method for measuring these protein clumps in the brain is urgently needed. We propose developing radioactively labeled chemical compounds that specifically bind to alpha-synuclein and tau aggregates in the brain and can be viewed by imaging methods such as PET scan.
Hypothesis:
We have developed compounds that specifically bind to the structurally altered and aggregated form of alpha-synuclein or tau and propose to produce similar compounds that have been optimized for use in PET imaging.
Study Design:
We will begin by assessing a compound for which we already have promising results for its safety in human subjects. We will then optimize the structure of our compounds for use as tracers that can be visualized by PET imaging. Finally, we will test our best candidate tracers in suitable model systems to determine whether they recognize and highlight the structurally altered forms of alpha-synuclein or tau.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
PET tracers that detect alpha-synuclein and tau, the proteins structurally altered in PD and related neurodegenerative disorders, would enable early diagnosis, the monitoring of disease progression and assessment of the effects of potential therapeutics in people with these disorders.
Next Steps for Development:
If our project is successful, we would conduct a clinical trial with our most promising alpha-synuclein tracer in people with PD. In addition, we would further develop our portfolio of novel and structurally optimized alpha-synuclein- and tau-specific tracers for preclinical and ultimately clinical testing.