Aging is one of the most important risk factors for Parkinson’s disease. To better understand how aging increases disease risk at both the cellular and molecular levels, researchers need human-relevant models that allow the study of disease mechanisms over time. In this project, Donega and De Vries will develop a brain organoid model that incorporates induced pluripotent stem cell (iPSC)–derived microglia and mimics key aspects of aging and Parkinson’s disease pathology.
Recent advances in the development of brain organoid models have created new possibilities to study brain diseases using patient-derived in vitro models. In Parkinson’s research, human midbrain organoids (hMOs) offer a physiologically relevant model. However, existing hMOs primarily resemble early embryonic brain development, making it challenging to model aging-related and late-stage disease processes.
The newly funded project aims to overcome these limitations by developing an in vitro model that mimic both molecular and cellular features of brain aging alongside hallmark Parkinson’s pathology. In collaboration with Elga de Vries iPSC-derived microglia will be incorporated into hMO to further increase their translational value.
The model will be used to investigate how aging influences Parkinson’s disease progression and to evaluate the effectiveness of stem cell–based therapeutic strategies for neural repair. The project will be carried out in collaboration with Wim Mandemakers at Erasmus MC.
Read more about the Dutch Parkinson’s Foundation (ParkinsonFonds)
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