Study Rationale: Seed amplification assays (SAA) are very effective in helping to diagnose Parkinson’s where the alpha-synuclein protein is involved. Using “spinal tap” fluid (CSF), SAA can tell if a person has Parkinson’s, but unfortunately can’t measure the amount of alpha-synuclein. This is important since measuring alpha-synuclein might tell us how severe a person’s Parkinson’s has become or if a new drug to treat Parkinson’s is slowing or even reversing disease. By modifying the standard SAA, we think it’s possible to measure alpha-synuclein in CSF, and possibly in blood or saliva. This we would do by replacing different components of the SAA with modified alpha-synuclein and a new dye that can simultaneously bind to and measure alpha-synuclein. This would generate a new SAA that would help us to track Parkinson’s progress and monitor treatments.
Hypothesis: Modifying the current SAA by labelling alpha-synuclein and using new alpha-synuclein dye will allow measurement of alpha-synuclein in various body fluids.
Study Design: We will use several different tissues including CSF, brain, and blood, to see if a new SAA can measure alpha-synuclein. Using brain and CSF from the same donor, we will measure alpha-synuclein and compare these results with the amount of pathology found in the brain of the same person to see if the results are directly related - we expect more alpha-synuclein in CSF to mean more alpha-synuclein pathology. We will then see if we can measure alpha-synuclein in blood and saliva with the assay and if the amount of synuclein relates to severity of Parkinson’s.
Impact on Diagnosis/Treatment of Parkinson’s disease: A new SAA would show severe the alpha-synuclein pathology might be within the brain or body. Having this information would help plan a persons’ treatment by seeing if they are likely to need extra support sooner rather than later. The SAA would also be able to monitor new treatments being used.
Next Steps for Development: A new SAA would need to be tested in bigger groups of people with Parkinson’s where symptoms have been monitored and recorded. This would allow the SAA to be carefully checked for accuracy, not only in diagnosis of Parkinson’s, but also that measurements reflect a persons’ treatment and progress.