Abstract

 

A brain organoid model to study Parkinson’s disease (and aging)

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting the aging population. Despite extensive research efforts for over a century, the disease is still incurable. The difficulty of capturing the human-specific and multifactorial nature of the disease in conventional in vitro models contributes to the disappointingly high failure rate of new candidate molecules in clinical trials. Recent advances in tissue engineering using human induced pluripotent stem cells (iPSCs) have allowed us to model key hallmarks of neurodegenerative diseases. Using this tool, we have developed methods to generate PD-patient-specific brain organoids. These organoids exhibit time-dependent dopaminergic degeneration and astrocyte alterations compared to controls, mirroring what is observed in human brain samples. Interestingly, we can incorporate also the aging component leveraging stem cell exhaustion of the neural progenitor used to generate the organoids. These data strongly support the use of 3D models to study complex cellular mechanisms underlying PD and for drug testing.