Serum L-ornithine-derived polyamines as indicators of Parkinson disease progression

Prior studies reported that biospecimen concentrations of L-ornithine-derived polyamines (ODPAs) and their metabolites differentiated Parkinson disease (PD) from healthy controls. We investigated ODPA metabolism in CSF and serum specimens from well-characterized, unmedicated PD patients to explore correlations with disease severity, progression, and PD clinical subtypes using data from Unified PD Rating Scale (UPDRS) assessments. We developed targeted assays for L-ornithine and the ODPAs putrescine, spermine, spermidine, and the polyamine metabolites N⁸-acetylspermidine and N-acetylputrescine. Biospecimens were sampled up to 22 months apart. In addition to investigating correlations between ODPA metabolism and PD severity, we modeled initial ODPA measurements for prediction of disease progression. Between specimen collections, mean summed UPDRS Activities of Daily Living scores increased from 8.5 to 13.4; mean summed UPDRS Motor Exam scores rose from 20.1 to 28.9 (for both, p < 0.001). During this interval, mean serum putrescine, spermidine, and spermine concentrations increased by 20%, 20%, and 32% (for all, 2-tailed t-test p < 0.023) though their CSF concentrations were unchanged. Initial serum N-acetylputrescine concentrations predicted disease progression for a subgroup of patients with gait disorder and postural instability. The marked increases of ODPAs as PD disease progressed suggest a relationship to PD pathogenesis. If these findings are validated, interrogating ODPA metabolism may offer an easily sampled indicator of disease progression for use in clinical trials.