Development of a predictive biomarker for Parkinson's disease

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Parkinson's disease (PD) affects ~7 million people globally with a projected doubling in cases by 2040. Currently, the annual cost to the NHS is £2,118 per patient with an annual economic burden of £20,123 per PD household. There is no disease-modifying therapy currently, but such therapeutics are in clinical trials. A major bottleneck in the conduction of clinical trials is the identification of patients at the earliest stages of the pathogenesis and the exclusion of disease-mimics. PD starts several years before clinical presentation. Identifying individuals in this prodromal phase would be optimal for clinical trials and eventual instigation of disease-modifying therapies. We have developed a blood test that predicts PD pathology based on serum measurements of neuronally-derived alpha-synuclein, the key pathogenic protein in >95% of cases. Specifically, we immunocapture extracellular vesicles expressing the neuronal antigen L1CAM (L1EV) and have developed microfluidic prototypes for highly effective on-chip L1EV isolation within 30min. We discovered that total L1EV associated alpha-synuclein levels are increased in the prodromal and clinical phase of PD using >1,000 samples across multiple cohorts. We now seek support to develop this platform as a standardised clinical test. We will refine the assay parameters and translate our microfluidic prototype into a device suitable for clinical practice, to be used in conjunction with highly sensitive downstream marker quantification. The final assay format will be tested in a deeply phenotyped longitudinal cohort of individuals at risk of developing PD or patients with different rates of disease progression.