Funded Studies
Study Rationale: Parkinson’s disease (PD) and other synucleinopathies are diagnosed based on symptoms and clinical testing. However, these tests can be inaccurate, and postmortem analysis reveals that 20 to 30% of people with PD are misdiagnosed. Blood tests for detecting alpha-synuclein, the main pathology of PD and Lewy Body Dementia (LBD), can facilitate more accurate diagnosis. Unfortunately, most of the alpha-synuclein found in the blood does not come from the brain. We propose to overcome this problem by capturing neuron-derived extracellular vesicles (NDEs), small lipid spheres secreted by neurons. Some of the NDEs that enter the bloodstream carry neuronal cargo, including alpha-synuclein.
Hypothesis: We hypothesize that the amount of alpha-synuclein within and on the surface of NDEs isolated from blood plasma neurons reflects changes in the brain and that this measurement can therefore be used to identify and potentially stratify different synucleinopathies, including PD, LBD and multiple system atrophy (MSA).
Study Design: NeuroDex has already developed and validated the methodology for isolating NDEs from blood plasma and produced a test for measuring the alpha-synuclein associated with these NDEs. Using these proprietary measurements, NeuroDex identified significant differences between healthy volunteers and people with PD or MSA (approximately 30 subjects per group). Now, we expand this investigation to two larger, well-established clinical cohorts. This study will be retrospective, meaning that the samples have already been collected; in total, we will test more than 500 subjects. This project will help us to determine the diagnostic utility of this new biomarker and further validate its quality.
Impact on Diagnosis/Treatment of Parkinson’s disease: A blood test for alpha-synuclein pathology could expedite diagnosis and selection of patients for clinical trials, and it could potentially serve to evaluate treatment response. Stratifying synucleinopathies can further aid in providing individuals with more accurate prognoses and in enabling precision medicine for the treatment of PD.
Next Steps for Development: This study represents the discovery phase in the development of NDEs as a biomarker for synucleinopathies. We will follow up with analytical validation in NeuroDex’s CLIA-certified lab and then large-scale clinical validation, ultimately leading to commercialization as a diagnostic test and a clinical trial biomarker.