An early diagnostic test to identify those with Parkinson’s disease (PD) and to intervene with therapies as early as possible is a critical unmet need. Recent studies have suggested that levels of the protein alpha-synuclein in peripheral nervous tissue (e.g., colon and cerebrospinal fluid) can distinguish people with PD from controls, maybe even before the onset of motor symptoms, and thus this could provide a diagnostic tool.
We will test three novel methods on accessible biosamples to see if these can provide simple, reliable diagnostic tools for PD in its early stages.
The Oxford Parkinson's Disease Centre has amassed a large, longitudinally followed cohort of 1,200 early PD patients, 300 controls and 300 at-risk subjects. We have collected ~200 peripheral biopsies (from colon, upper GI tract and prostate) from these patients taken for various reasons prior to their PD diagnosis, and we have taken cerebrospinal fluid (CSF) samples from a subset (100 PD, 20 controls, 20 at-risk).
We have adapted two techniques — paraffin embedded tissue blot and proximity ligation assay — that are more specific and sensitive methods than conventional immunohistochemistry to detect early, disease-associated alpha-synuclein deposition. We are also developing real-time quaking induced conversion to specifically assess the aggregation of alpha-synuclein in CSF.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
With a successful biomarker we will have a greater window to conduct therapeutic trials of disease modification and perhaps even a possibility to prevent the disease in those destined to develop Parkinson’s.
Next Steps for Development:
If successful, these techniques could provide simple, reliable diagnostic tools for PD at the earliest stages, as well as useful ways of monitoring disease progression and the effectiveness of future neuroprotective treatments of PD.