Alpha-synuclein is a protein that is found in nerve cells of patients with PD and therefore provides a potential target for methods designed to monitor the disease process in PD. We plan to modify a small protein custom made to tag alpha-synuclein so that we can develop a brain imaging radiotracer for PD diagnosis and progression. This imaging tool could also be used to help understand how proteins like alpha-synuclein may contribute to the cause of PD.
Our international collaboration will combine the work of Omar El-Agnaf who has developed and characterized small molecules that bind alpha synuclein with the experience and expertise in radiotracer development at the Institute for Neurodegenerative Disorders (IND). Working together we will modify these alpha-synuclein binding small molecules to make them suitable as brain imaging radiotracers. Radiotracers are molecules that have a radioactive isotope attached. This enables the compound to be tested using either SPECT or PET imaging, brain imaging techniques that allow us to measure how much radiotracer is in the brain and where is it located in the brain. We plan to test this alpha-synuclein binding radiotracer in animal studies to assess whether this radiotracer is safe and may be useful. If successful we would plan to test this radiotracer in studies of both healthy research subjects and PD patients.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Developing an alpha-synuclein imaging tool would have dramatic impact on PD diagnosis and treatment. Since alpha-synuclein is deposited in nerve cells in PD very early in disease and appears to progressively increase, a reliable and accurate method to image alpha synuclein would potentially enable early and accurate diagnosis (possibly even before typical PD symptoms), monitor PD progression, and allow testing of drugs that might reduce or prevent alpha-synuclein deposition in PD.
We will test a new strategy to develop an alpha-synuclein imaging tracer and will learn whether this approach may provide a critical tool for PD research.
We have examined whether a small peptide engineered to bind alpha synuclein can be labeled with 123I and or 18F to develop a radiotracer targeting alpha synuclein. The lead peptide has been labeled and injected into non-human primates scanned with SPECT. Preliminary data suggest brain uptake but no specific binding has been demonstrated. Additional work will determine if there is specific brain uptake.