Study Rationale: In both Parkinson's disease and multiple system atrophy (MSA), the protein alpha-synuclein becomes altered, resulting in the accumulation of clumps of aggregated alpha-synuclein in the brain. These clumps impair the function of brain cells, causing neurodegeneration. New, more precise diagnostic tests that allow these alpha-synuclein aggregates to be measured in the brain are urgently needed. Such tests could aid disease diagnosis and help to measure the effects of experimental therapies that aim to reduce alpha-synuclein aggregates. PET imaging could be used for this purpose, involving the use of radioactively labelled chemical compounds which bind to aggregated alpha-synuclein in the brain.
Hypothesis:We demonstrated that MODAG-009 binds to aggregated alpha-synuclein and its first use in patients appeared to be both safe and promising. The proposed trial aims to confirm the safety of administering MODAG-009 and its effectiveness in measuring alpha-synuclein aggregates in patients.
Study Design: The safety of MODAG-009 will be assessed in healthy volunteers and patients with Parkinson’s disease or MSA. To this end, we will clinically monitor the well-being of all study participants by physical and neurological examinations and standardized questionnaires. In addition, vital signs and blood samples will be analyzed. Furthermore, we will test if alpha-synuclein aggregates can be visualized in the brains of these patients by MODAG-009. This will be done by PET imaging using radioactively labelled MODAG-009. Finally, we will analyze the obtained images to see if there are differences between patients and healthy volunteers, and between PD and MSA patients.
Impact on Diagnosis/Treatment of Parkinson’s disease: MODAG-009 could be used as a tracer in PET scans to detect alpha-synuclein aggregates in patients with Parkinson's disease or MSA. This would enable the early and differential diagnosis of these diseases, as well as monitoring their progression and the effect of potential therapies that aim to reduce alpha-synuclein aggregates in human patients.
Next Steps for Development: If the project is successful, the next step will be to administer MODAG-009 to more patients. Further confirmation of MODAG-009’s ability to visualize and measure alpha-synuclein aggregates in the human brain would eventually enable this novel PET tracer to be made available to all patients worldwide as part of routine clinical practice.