Human in vitro Opto-electrical Parkinson´s Disease Model with a Gut Feeling - HOPE

Europe is facing a major challenge with its ageing population and associated increase in neurodegenerative diseases (NDD).

Parkinson´s disease (PD), the 2nd most common NDD, is associated with tremor and loss of motor functions due to progressive degeneration of dopaminergic neurons in the nigrostriatal pathway (NSP), which ultimately can lead to memory loss and dementia. There is no cure for PD and existing therapies only relieve symptoms.

There is a lack of understanding of the underlying mechanisms of PD, partly because existing animal models fail to reproduce key features of the human biology.In HOPE we will resolve some of the fundamental questions related to neurodegeneration and treatment of PD. This will be enabled by developing a human in vitro opto-electronic PD disease model with a “gut feeling”.

We will model the NSP, using optogenetically modified human pluripotent stem cell (hPSC)-derived neurons and brain organoids (BOs), linked to a simplified “Gut” in compartmentalised microfluidic chips with integrated optical control and real time dopamine (DA) sensing.

A connectoid will be formed by precise spatial arrangement of two regionally specific BOs, representing the NSP, connected via hydrogel tracts promoting axonal pathfinding, functional connection, and DA signalling. In this way, a native neural pathway will be created in vitro in a physiologically and anatomically relevant system.

This beyond what is possible with any existing PD disease model.