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Funded Studies

Evaluating Polyamines as Biomarkers for Parkinson’s Disease

Study Rationale: One of genes associated with Parkinson’s disease (PD), ATP13A2, regulates the levels of polyamines in the lysosome, an acidic compartment of the cell. Polyamines are neuroprotective, and changes in polyamine levels in blood plasma have been observed in people with PD. This observation suggests that polyamines may have potential to serve as disease biomarkers. At the same time, several lipids have also been proposed as PD biomarkers. Because GBA1, the major genetic risk factor for PD, controls the function of lysosomes by degrading lipids, it is possible that ATP13A2 and GBA1 may influence each other.

Hypothesis: We hypothesize that there is a correlation between the changes in specific polyamines and lipids in the plasma of patients with PD, which may point to cross-talk between PD pathways that converge at the lysosomes in the cell.

Study Design: We will collect plasma samples of people with sporadic PD and those with GBA1 mutations from existing cohorts that are supported by MJFF. In these samples, we will measure the polyamine levels using mass-spectrometry techniques, and correlate them with lipid concentrations that have been measured previously. Using statistical methods, we will evaluate the changes in the polyamines and determine whether and how they correlate with changes in lipids.

Impact on Diagnosis/Treatment of Parkinson’s disease: Information regarding the plasma polyamine and lipid status may be used for the diagnosis of PD and may be valuable for patient stratification in clinical trials for treatments targeting polyamine or lipid pathways.

Next Steps for Development: Following this pilot study, we will evaluate the biomarker potential in a larger cohort and at different disease stages. If a correlation between polyamines and lipids is established, the modulation of polyamine levels may be considered for therapy.


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