Tailored pharmacotherapy monitoring in Parkinson’s disease and Schizophrenia using a rapid and sensitive α-Synuclein assay

Abstract

Background

While Parkinson’s disease is a low dopamine neurodegenerative disorder, Schizophrenia is considered a high dopamine psychiatric disorder. Pharmacological interventions that are directed to normalize dopamine concentrations in the mid-brain for an extended duration lead to unintended consequences. Parkinson’s disease patients experience psychosis, and Schizophrenia patients develop extra-pyramidal symptoms due to dopamine levels overshooting their physiological range. An objective monitoring technique is therefore required for better therapeutic efficacy in these two neurological diseases.

Methods

A rapid and sensitive assay for α-Synuclein based on magnetic enrichment and enzymatic fluorescent signal generation was developed. This assay has been benchmarked with conventional ELISA and validated in 53 CSF and 36 serum samples.

Results

Developed assay from an experimental perspective has a sensitivity of less than 10 pg/mL; requires a turnaround time of 45 mins; and uses 2 µL of CSF/serum fluid samples to quantify alpha synuclein. From a utility perspective, the assay showed (a) a two-fold linearity across clinical phenotypes of Parkinson’s disease, neurological controls, and schizophrenia patients; (b) variation between the naïve and treated patients; (c) correlation with severity of the disease. From a diagnostic perspective, the serum-based assay had a 100 % specificity and a minimum of 67 % sensitivity in differentiating naïve patients from treated patients; the CSF/serum-based assays had a minimum of 91 % specificity and a minimum of 85 % sensitivity in differentiating patients from neurological controls.

Conclusions

The developed assay can be used to quantify alpha-synuclein in serum and CSF samples, thereby setting a translational platform for diagnosis, prognosis, and monitoring pharmacotherapy patients with Parkinson’s disease and Schizophrenia.