Parkinson’s disease (PD) is the second most common neurogenerative disorder in the world affecting an estimated 7 million people globally. Its global prevalence is expected to double over the next 20 years, partly due to our increasingly ageing population. PD is caused by α-synuclein (α-syn) accumulation and aggregation inside neurons, especially dopamine-producing neurons, causing their death. It is typically preceded by a long prodromal phase, where individuals do not fulfil diagnostic criteria for PD but start to exhibit non-motor symptoms such as a sleep disorder called REM sleep behavioural disorder (RBD).

Early PD diagnostic remains challenging

Currently, PD is diagnosed once a decline in motor symptoms has been recognised, with no single diagnostically conclusive test. By the time PD has progressed to the point whereby motor symptom deterioration is visible, up to 70% of dopamine neurons may have been lost. Additionally, the non-specific nature of the symptoms observed in early diagnosis results in PD often being missed or misdiagnosed. The development of efficient methods to assay key biomarkers in the earliest stages of PD will undoubtedly underpin therapeutic intervention when disease-modifying therapies become available.

α-synuclein is a promising PD biomarker

Current methods to measure α-syn concentration in patients biological fluids are either not efficient or not suitable in most clinical settings because this protein is produced by various cell types including red blood cells. An alternative approach is to quantify the concentration of α-syn released from neuronal tissues, such as neuron-derived exosomes, but the isolation of exosome subpopulations in complex biological fluids remains as of today challenging.

Efficient isolation of exosomes from contaminants

Researchers and clinicians at the University of Oxford have developed a new immunocapture assay that efficiently isolates exosomes from patients’ serum. Using this assay, they established that release of neuronal exosome-associated α-syn is an early pathophysiological response before the clinical diagnosis of PD. When used in combination with the levels of clusterin in neuronally-derived exosomes, PD and subjects with RBD who are at risk of developing PD could be distinguished from controls or patients with atypical Parkinsonism.

This technology was tested and validated in a cross-sectional study of 735 patients from four independent cohorts.

Commercialisation

Oxford University Innovation is looking to hear from parties interested in developing or licensing this technology. This invention is the subject of two patent applications (PCT/GB2020/052872 and PCT/GB2020/052871).