Study Rationale: Synuclein seeds detected in cerebrospinal fluid are the earliest sign of Parkinson’s disease (PD) identified to date. CSF has a simpler composition than blood or saliva. To detect these synuclein seeds in complex fluids, one has to extract the seeds from the rest of the fluid. Here, we propose a novel and simple way to extract these aggregates from complex fluids like serum, plasma, and saliva. These extracted seeds will then be analyzed using the synuclein seed amplification assay (synSAA), which is the same test that detect these aggregates in CSF. If this method were to be successful, the synSAA could be offered to patients using a non-invasive sample.
Hypothesis: We hypothesize that a dye called Thioflavin T (ThT), which is a reagent to see synuclein aggregates when they are present in large quantities, can bind synuclein seeds at very low concentration in biological samples. If true, we could then use ThT to extract seeds from complex matrices.
Study Design: We will perform proof of concept studies using CSF samples known to have synuclein seeds (CSF+) to test if we can capture the synuclein seeds from CSF. We will then evaluate capture when mixing CSF+ with complex matrices like serum, plasma, white cells, saliva, skin homogenate, etc., and see if these complex samples impede the capture of the synuclein seeds. If the capture fails, we will make changes to the process to overcome the interference of the sample. Lastly, when we know that the optimized capture can overcome the interference from the sample, we will evaluate actual samples from persons living with PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: If our hypothesis is correct, then we could make several non-invasive biological samples compatible with the synSAA, the identification of people at-risk or with very early symptoms of PD. This could open a new window for therapeutic intervention aimed at slowing down the disease. This would be a game-changer for the way PD is diagnosed, managed, and potentially treated.
Next Steps for Development: The next step of this study is the analysis of samples from a large cohort of participants and compare the results with CSF. If the accuracy of the non-invasive test were to match CSF, then the next step would be the transfer of the procedure to Amprion’s clinical laboratory to start formal validation of the assay to offer it commercially.