Polyamine Biomarkers of Parkinson's Disease Progression
LeWitt PA, Hong L, and Patil R. Polyamine Biomarkers of Parkinson's Disease Progression. Mov Disord 2022; 37:S16-S17.
Objective: To investigate progression biomarkers of PD, we measured concentrations of polyamines and metabolites in CSF and serum samples collected twice during the DATATOP study.
Background: Polyamines are small, positively charged molecules with wide systemic distribution and multiple intracellular functions. Their roles include regulating gene transcription/translation, stabilization of polynucleotides, interactions with multiple enzymatic activities, and protective responses against oxidative stress. Several reports have described that PD biospecimens (versus controls) show altered concentrations of various polyamines and their metabolites. However, sequential changes in polyamines related to disease progression or severity haven’t been investigated.
Methods: We studied DATATOP participants (male and female) whose matched CSF and serum samples were collected at baseline and up to 24 months later. In the trial, the 40 selected subjects had received only a placebo. At end-of-study, all were judged to have >90% certainty of a correct PD diagnosis. Targeted high-precision assays were developed using ultrahigh performance liquid chromatography coupled with tandem mass spectrometry. We measured the polyamine precursor L-ornithine, the 3 human polyamines (putrescine, spermine, and spermidine), and two polyamine metabolites (N8- acetylspermidine and N-acetylputrescine).
Results: Two-tailed t-tests compared assay results from Baseline End- of-Study. In CSF, none of the 6 measured compounds revealed significant or nominal changes in concentration. However, measurements in serum revealed significant increases in concentrations of putrescine (9.63 11.54 ng/ml; 20%; p=0.023), spermidine (20.18 24.16; 20% ; p=0.021), and spermine (7.28 9.56; 31% ; p=0.014)
Conclusions: Prior studies reported that serum and CSF concentrations of certain polyamines and metabolites distinguished PD from controls and other neurological disorders. Our observations in unmedicated, mildly affected PD patients show associations between PD progression and significant elevations in serum concentrations for each of the 3 polyamines. Further analysis is ongoing to investigate correlations between polyamine changes and UPDRS motor scores, PD progression data, age, and other relevant demographic and clinical features.
Funding: The Sastry Family Foundation Endowment, Wayne State University School of Medicine, and the Michael J. Fox Foundation for Parkinson’s Research.