Human Stem cell-based technologies to model PARKinson’s disease and drive patient-specific cell therapy

Loss of dopaminergic (DA) neurons in midbrain underlies motor dysfunction in Parkinsons disease (PD).

PD is one of the most challenging neurodegenerative diseases to study due to the limitations of existing model systems in recapitulating its complex etiology resulting from individual risk variants, distinct genetic and epigenetic backgrounds, and age-related environmental triggers.

The SPARK project (Human Stem cell-based technologies to model PARKinsons disease and drive patient-specific cell therapy) will use induced pluripotent stem cells reprogrammed from PD patient-derived somatic cells as well as from age- and sex-matched healthy individuals to model key aspects of DA neurodegeneration.

Advanced human stem cell-based technologies including brain organoids and cell transplantation will be exploited to recreate functionally mature human DA tissue in an ad hoc disease-like environment.

A single-cell sequencing approach will be used to obtain molecular insights into PD etiopathogenesis and the pathological mechanisms responsible for DA neuron degeneration.

Lastly, gene editing in a patient-specific genetic background will be performed to create an autologous source of healthy DA neurons reverted from the disease-related phenotype.

These cells will be pre-clinically validated in a PD rat model, with a view to ultimately achieving autologous cell replacement treatments for PD.