Stem cell-based treatments for Parkinson’s disease: Novel concepts and future therapies

Neurodegenerative diseases are debilitating conditions that result in dysfunction and loss of nerve cells.

The brain has a very limited capacity for self-repair, and there is an unmet need for finding new therapeutic strategies.

My team has been successful in generating dopamine (DA) neurons from pluripotent stem cells, and our work have been a main driving force for first-in-human clinical trials in Parkinson’s Disease (PD). This proposal is designed to capture the momentum in the field.

It strives to integrate transcriptomic and connectomic analysis at the single cell level in advanced xenograft models to provide unique insights into how human DA neurons mature and integrate after transplantation.

The findings will be implemented to improve control of cell fate specification, and to explore the ability to extend on the cell replacement concept and build strategies for more complete circuitry repair and reconstruction. Moreover, cell reprogramming has opened up the possibility for autologous grafting using patient-derived cells.

As an important development in this field, we will explore if patient-derived cells are more prone to develop pathology after transplantation, and if so device gene correction or gene editing approaches to create healthy versions of cells for transplantation.

Combined, the results from these projects will lead to novel strategies for brain repair with focus on PD, but applicable also for regenerative approaches in other neurological disorders.