Study Rationale: Our new MJFR14-proximity ligation assay (PLA) technique has demonstrated an ability to detect disease-associated aggregates of alpha-synuclein in brain tissue previously considered unaffected by abnormalities associated to Parkinson’s disease. We want to test if this novel technique can be used as a disease biomarker in patients using blood and skin samples. If successful, this could be used to quantify treatment responses in clinical trials.
Hypothesis: We want to test if MJFR14-PLA positive signals are present in skin biopsies, blood cells and extracellular vesicles isolated from blood of patients with Parkinson’s disease.
Study Design: The optimization and validation phase will test different MJFR14-PLA formats on patient skin biopsies, blood cells and total and neuron-derived extracellular vesicles from blood. A PLA format targeting soluble alpha-synuclein aggregates will also be developed. The validation will be performed on skin biopsy cohorts from Parkinson’s disease, dementia with Lewy bodies (DLB) and controls, as well as blood-based samples from DLB and control patients. Upon successful validation, the sensitivity and specificity will be tested in the established S4 cohort for skin samples and blood from a DLB and REM Sleep Behavior Disorder cohort. This will determine if the assays are ready for clinical studies.
Impact on Diagnosis/Treatment of Parkinson’s disease: Aggregation of alpha-synuclein plays a pivotal role in Parkinson’s disease and is the target for multiple therapies being tested in clinical trials. A successful outcome of this project will facilitate studies of treatment responses in patients by allowing consecutive samples to be analyzed from the patient during the treatment.
Next Steps for Development: The next step will be to make optimized protocols and facilitate generation of test kits that can be distributed to investigators in the clinic and pharma.