Longitudinal immunophenotyping to track motor progression in Parkinson’s Associated with a TH mutation

Abstract

Background and Objectives: PD is the second most common neurodegenerative disorder and the fastest growing. Genetic factors account for ∼15% of cases. Despite some consistency in symptoms across idiopathic and genetic PD cases, tracking progression and treatment response remains an important challenge especially in the development of new therapies. There have been many traditional approaches to tracking including DaTscan imaging, cardiac 123I-MIBG scintigraphy, MRI, CSF analysis, and following clinical symptom progression. Methods: Our previous work showed that peripheral blood mononuclear cells (PBMCs) expressing dopamine transporter (DAT) and tyrosine hydroxylase (TH) in PD patients may correlate with disease progression and with the response to treatment with levodopa. We describe a single case longitudinal follow up of a 40-45-year-old woman with PD who carried a heterozygous TH mutation. We assessed her clinical features over 18 months with DaT scans and immunophenotyping of her PBMCs. Her data were compared with idiopathic PD (n=130 subjects, both sexes) and healthy controls (n=80, age/sex matched). Results: The results revealed a rise in DAT+ immune cells which occurred coincident to documented worsening of her UPDRS-III motor scores. Unlike idiopathic PD patients, following levodopa therapy, the TH+ immune cell levels remained elevated, despite UPDRS-III score improvement. Discussion: The longitudinal immunophenotyping in this PD patient with a TH mutation suggested that DAT+ and TH+ PBMCs could be candidate biomarkers for PD progression and possibly treatment effectiveness. This study provides proof of concept to explore this approach to investigate immunophenotyping in PD progression.