Patient Specific Brain Organoids for In Vitro Modeling of Parkinson's Disease

Brain organoids are self-assembled three-dimensional cellular aggregates with cell types and tissue architectures that resemble the embryonic human brain. As they recapitulate many key features of early human brain, they have emerged as novel model systems to investigate human brain development and disorders in vitro. More recently, region-specific brain organoids have come forward as tools to study diseases and processes affecting specific parts of the brain. In this regard, midbrain organoids are essential to study one of the most affected regions in Parkinson’s disease, the midbrain. We make use of Parkinson’s disease patient specific midbrain organoids for the discovery and development of effective drug candidates, which target neurodegeneration. These models are complex and recapitulate many features of the human midbrain, including the presence of dopaminergic, glutamatergic, GABAergic and serotonergic neurons, astrocytes, oligodendrocytes, microglia and other cell types. We focus on disease relevant phenotypes including the loss of dopaminergic neurons, the appearance of alpha-Synuclein aggregates and neuroinflammation. Our phenotypic approach allows for the detection of disease associated conditions as well as their amelioration after drug treatment. Importantly, this is not limited to screening for efficacy of novel small molecule drugs, but can also cover the testing of anti-sense oligonucleotides, peptides or other therapeutic approaches. We are committed to the further development of our models and the improvement of assays and computational tools to perform deep phenotyping of our models to better detect cellular defects and their rescue following compound treatments.

Learning Objectives: 

1. Describe the concept of organoids and midbrain organoids.

2. Certify the use of 3D in vitro culture models for modeling complex neurodegenerative diseases.

3. Illustrate the application of the organoid technology for drug screening.