Year 4/NCE

During our project we achieved several scientific goals. Our project was to utilize Parkinson’s disease patient derived stem cells to model their disease. The particular cells we used were derived from patients with mutations in the LRRK2 gene, which is the most common cause of inherited Parkinson’s disease. At the end of our funding we can report proficiency in induced pluripotent stem cell (iPSC) differentiation to dopaminergic cells protocols in a workflow that allows higher throughput analysis. Dopaminergic cells are types of cells lost in the brain in Parkinson’s disease and if we study cells from patients with this mutation it will likely yield insight into the processes of disease onset and progression. This funding enabled collaboration with the laboratory of Dr. Schuele here at the Parkinson’s Institute to use cells generated in other CIRM funding (ETI-0246 and RT2-019665). The cell lines we used were edited to “fix” the genetic mutation in the LRRK2 gene and also to delete (or knockout) the LRRK2 gene. We used these cells and determined that loss of LRRK2 imparts an increased propensity for dopaminergic differentiation potential for knockouts over mutant and wild-type cells. Also, we determined that LRRK2 inhibitors do not negatively impact the generation of dopaminergic cells in cell culture modeling. We will continue to unravel the roles of LRRK2 in Parkinson’s disease using these pertinent, patient centric models.