Changes in lipid metabolism have been strongly associated with Parkinson’s disease (PD). Lipids have the potential to be important biomarkers for PD, but the lack of appropriate tools to measure total lipids (lipidome) in human dopamine neurons has limited advances in this field. Here, we propose to develop a novel unbiased and high-throughput single cell assay to determine total lipids. This will allow us to identify and validate lipid metabolites in dopamine neurons, which may serve as biomarkers for PD.
We will determine if the analysis of the lipid composition of human dopamine neurons affected in PD can result in the identification of new lipid biomarkers.
We will start by optimizing a high-throughput assay already available in our lab to comprehensively characterize the lipid composition of human dopamine neurons derived from stem cells. This will be done at single-cell level using dopamine neurons engineered to carry multiple PD-associated genetic mutations. Comparison to control dopamine neurons will reveal lipids with the potential to become biomarkers for PD. These lipids will be further validated as potential biomarkers using sporadic PD patients’ derived dopamine neurons.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The identification of lipid biomarkers could lead to a new opportunity for early diagnosis of PD and to the development of new therapies involving lipid metabolism.
Next Steps for Development:
The next steps will involve the validation of these results in accessible biofluids (e.g. blood and CSF) and the use of these results for improved patient stratification for future clinical trials.