Developing a Molecular Imaging Tool That Binds to Alpha-Synuclein and Inhibits Its Formation
Improved Biomarkers & Clinical Outcome Measures, 2016
Amyloid fibrils play a key role in Parkinson's disease (PD). Studying their formation from self‐assembled aggregates (protein clumps) would help aid the development of a valuable diagnostic tool. Despite progress in understanding these processes in a test tube, visualization through an imaging approach has not yet been fully achieved. We will develop a contrast agent with protective effects based on a molecule that has recently been proposed to interact with related compounds.
This project aims to develop a novel type of magnetic resonance imaging (MRI) reporter (tag) that specifically binds to alpha‐synuclein, as a disease‐modifying molecular target for Parkinson's, and inhibits further fibril formation to interrupt the disease progress at an early stage.
This project relies on the recently developed concept of xenon biosensors (special sensors that detect molecular changes), which enable MRI scans to capture images at unprecedented levels of sensitivity. We will synthesize a novel sensor type where the molecular container can trap xenon or alpha‐synuclein to change its signal at the onset of fibril formation and inhibit further progression. This study will explore the MRI capabilities of such a sensor in cell cultures specifically used in PD research. MRI detection will be co-validated with other imaging methods to optimize the tool prior to clinical testing.
Impact on Diagnosis/Treatment of Parkinson’s disease:
This project has a two-fold impact: we will gather information on the therapeutic effect proposed for this technique, and we will use the tool to design a contrast agent that is sensitive to the early onset of PD before amyloid fibrils develop.
Next Steps for Development:
We plan for the rapid translation of the tool into preclinical testing upon successful completion of this study. Such a step will foster improvements in drug development that focus on early molecular events during the onset of PD in preclinical models. Depending on these findings, this tool may eventually lead to clinical applications in humans.
Group Leader Molecular Imaging at Leibniz-Institut für Molekulare Pharmakologie (FMP)
Location: Berlin, Germany