A PRECISION CELL REPLACEMENT STRATEGY FOR PARKINSON’S DISEASE
|Title||A PRECISION CELL REPLACEMENT STRATEGY FOR PARKINSON’S DISEASE|
|Sponsor||European Research Council - Advanced Grant (ERC-AdG)|
Associated cell lines
Proof-of-concept clinical studies using human midbrain tissue for transplantation have shown that replacement of midbrain dopaminergic neurons (mDAs) can change the course of Parkinson's disease (PD). Human pluripotent stem cells (hPSCs) are currently used to generate mDAs for cell replacement therapy in clinical trials. However, single-cell RNA-sequencing analysis of these preparations revealed that they comprise a complex mixture of cell types, including mDAs but also fibroblast-like cell types and serotonin neurons, the latter thought to drive dyskinesias. Selective generation of A9/substantia nigra neurons for PD cell replacement therapy remains thus a major challenge. Here I propose to identify how human adult A9 neuorns are generated and based on that knowledge develop a novel cell type-specific precision cell replacement therapy for PD.