Study Rationale: Parkinson’s disease (PD) is a progressive brain disorder characterized by the loss of dopamine-producing neurons. OrganoTherapeutics has developed advanced midbrain organoid models using cells from PD patients with a specific genetic mutation (LRRK2-G2019S). These brain organoid models mimic key features of the disease, including neuron loss and inflammation. By including immune cells (microglia), these organoids offer a more complete representation of the disease environment and can be used to study how potential drugs affect PD.
Hypothesis: This study aims to determine whether treating patient-specific midbrain organoids with LRRK2 inhibitors can reverse Parkinson’s disease-related changes and provide a model suitable for drug discovery.
Study Design: OrganoTherapeutics will use midbrain organoids made from cells of PD patients with the LRRK2-G2019S mutation. These organoids will be treated with two different types of LRRK2 inhibitor drugs. We will then measure dopamine levels, neuron survival, and inflammation markers to see if the drugs can reduce PD symptoms in the organoids. We will also examine how these drugs affect specific biochemical pathways in the cells.
Impact on Diagnosis/Treatment of Parkinson’s disease: This research could lead to a powerful new model for testing Parkinson’s treatments, helping to identify effective drugs faster and more accurately by mimicking the disease in the lab using patient-specific cells.
Next Steps for Development: If successful, the organoid model could be used broadly in preclinical testing of new PD drugs. Future steps may include adapting this platform for other genetic forms of PD and moving promising drug candidates toward clinical trials.