Scientists model Parkinson’s disease in midbrain organoids

A research group around SysMedPD member Jens Schwamborn advances experimental in vitro models to study Parkinson’s disease mechanisms and elucidate unexplored aspects of this neurodegenerative disorder. They presented their findings recently in the paper “Modeling Parkinson’s disease in midbrain-like organoids”, published in npj parkinson’s disease.

One of the main constraints in neuroscience and in the modeling of neurodegenerative diseases is the lack of modeling approaches that reflect the complexity of the human brain. The current in vitro disease modeling approaches are typically conducted with cultures of neurons grown under two-dimensional (2D) conditions. However, 2D cultures neglect physiologically relevant characteristics like the interaction between glia cells and neurons in a spatially organized microenvironment.

Recently, a new class of 3D in vitro models has been developed to compensate for this deficit, the so-called organoids. Organoids are self-organized three-dimensional tissue cultures that are derived from stem cells. They offer the opportunity to investigate the development of human organs in vitro and have a tremendous potential for in vitro disease modelling.

The objective of the scientists was to generate 3D organoids that resembled the complexity of the human midbrain, the region of the brain that is affected in Parkinson’s disease.

In their article they report an efficient and reproducible method to derive these midbrain organoids from Parkinson’s disease patients. The midbrain organoids recapitulated key features like spatial organization, electrophysiological activity and dopamine secretion. Importantly, patient specific midbrain organoids show indications for reduced amounts of dopaminergic neurons, one of the actual hallmarks of Parkinson’s disease. Therewith, these midbrain organoids represent a novel state of the art system for in vitro modeling of Parkinson’s disease and hold great potential for future research and development.

The full paper is available here.