Defining Mechanisms in Different Brain Cells that Drive Progression in Parkinson’s Disease

Study Rationale: The death of dopamine-producing neurons is the defining feature of Parkinson’s disease (PD), leading to the motor symptoms characteristic of the disorder. Given this obvious connection, much research, including disease modeling and drug development, has focused on this cell type. However, recent studies suggest that oligodendrocytes — a non-neuronal type of helper cell that supports the health and activity of neurons — may play a significant role in the onset and subsequent progression of PD, and may be affected prior to the dopamine-producing neurons associated with the disease.

Hypothesis: We hypothesize that oligodendrocytes may cause or modify the pathology of dopamine-producing neurons and thus contribute to the progression of PD through biological mechanisms that have yet to be uncovered.

Study Design: This study will use cells that have been reprogrammed from skin cells, known as induced pluripotent stem cells, obtained from patients with PD. We will convert these cells into either dopamine-producing neurons of oligodendrocytes and explore the health of these cells individually and how they interact when grown together in cell culture. To accomplish this, we will use a range of imaging techniques to visualize the behavior of the cells and a number of techniques to discover molecular pathways that are altered in disease.

Impact on Diagnosis/Treatment of Parkinson’s disease: Currently, we have no cure or treatments that slow the underlying progression of PD. By focusing on oligodendrocytes, which have received little attention until now, and examining their interactions with dopamine-producing neurons, we hope to uncover novel pathways and targets for therapeutic intervention.

Next Steps for Development: Characterization of oligodendrocytes and neurons will be linked to clinical outcome data from the individuals from which the cells were derived. This study will also identify potential targets for therapeutic intervention in oligodendrocytes and neurons and establish a preclinical platform for screening and investigating the mechanism of potential therapeutic compounds.