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Characterization of PET Tracers for Alpha-synuclein and 4R Tau

Study Rationale:
Parkinson’s disease (PD) is a brain disease characterized by slow movement, rest tremor and stiffness. In most cases the underlying cause is an aggregation of a protein called alpha-synuclein. If it were possible to see these harmful aggregations of alpha-synuclein in living brain, it would be of high importance for the diagnosis of PD and also for the development of new treatments to stop disease. The challenge is to develop a tool, which visualizes the aggregated alpha-synuclein in the brain of people who have Parkinson’s and those who will develop PD. A realistic approach is a “radiotracer for alpha-synuclein” — detectable with a method called positron emission tomography (PET-imaging).

As we have already produced compounds, which detect alpha-synuclein aggregates in low concentration (sensitivity) and specificity (that is they do not detect other proteins) in the test tube, we now characterize the most promising alpha-synuclein-tracers in pre-clinical models of Parkinson’s disease for their sensitivity and specificity before we investigate in humans.

Study Design:
We, a uniquely composed group of theoretical chemists, radiochemists, neuroscientists, neurologists and nuclear medical experts combine our knowledge and different methods.  We start by using artificial intelligence and screen and optimize new radiotracers. These are then chemically synthesized and tested in pre-clinical models of Parkinson’s disease, in postmortem human tissue and in living people with PD. Both the living pre-clinical models with Parkinson’s-like brain changes and the people with PD are investigated by PET-imaging for visualizing the radiotracers. This study design allows feedback-and-validation loops for further optimization until a radiotracer with unprecedented performance is obtained. By this approach we predict a breakthrough in Parkinson’s research.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
A radiotracer for alpha-synuclein combined with PET-imaging demonstrates the cause of PD (aggregated alpha-synuclein) in the brain not only when Parkinson’s symptoms are already present, but also in people who likely will develop PD. In both groups the alpha-synuclein radiotracer would improve diagnosis and help assess effects of therapies to potentially stop the progression of PD.

Next Steps for Development:
After one or several radiotracers for aggregated alpha-synuclein show convincing results in the pre-clinical PD models and in the pilot human studies on people with PD, one next step is a detailed characterization of the selected compounds for routine diagnostic clinical use. A second step is a study on people who look like Parkinson’s patients, but do not have aggregations of alpha-synuclein in the brain.


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