Study Rationale:
Research studies have yet to clearly explain whether alpha-synuclein oligomers -- clumps of protein alpha-synuclein -- in biologicals fluids can be used in clinics as measures of Parkinson's disease (PD). While there are many possible reasons for this lack of clarity, extensive testing of new critical raw materials, such as monoclonal antibodies, in biosamples, along with the development of new experimental setups (assays), might provide a solution.
Hypothesis:
The goal of this study is to determine whether measuring alpha-synuclein oligomers in cerebrospinal fluid (CSF) biosamples with new antibodies could aid in the diagnosis of Parkinson's, patient management or clinical trials.
Study Design:
All steps of the project, including the evaluation of antibodies, optimization of biosample collection and storage procedures and the design of assays, will be carried out at the same time and implemented in additional projects in case of documented clinical usefulness.
New monoclonal antibodies will be evaluated using brain biosamples from people with synucleinopathies (PD and Lewy Body dementia). Antibodies selected at that stage will be used to design assay prototypes for the testing of CSF samples. Finally, the resulting assay prototype(s) will be evaluated using biosamples from two well-characterized groups of people. If this evaluation is successful, we will continue to develop this assay with a goal of eventually integrating it into the field of Parkinson's disease medicine.
Impact on Diagnosis/Treatment of Parkinson's Disease:
This study will indicate whether analyzing alpha-synuclein oligomers in CSF can support diagnosis (e.g., early identification, diagnosis, prognosis and progression) or clinical trials (e.g., division of participants into study groups and monitoring of treatment efficiency).
Next Steps for Development:
If successful, the prototype assays will be further developed and tested according to regulatory guidance for future commercialization as a companion diagnostic, i.e., a test that provides information necessary for the best use of the corresponding drug. The inclusion of alpha-synuclein oligomers in the official guidelines for diagnosis of Parkinson's disease would also be possible at that point.