Project description
Stem cells and gene editing for new treatment for Parkinson’s disease
Parkinson’s disease (PD) involves loss of dopaminergic (DA) midbrain neurons causing motor dysfunction. As one of the most challenging neurodegenerative diseases to study, the EU-funded SPARK project will use stem cell-based technologies to model PD and develop patient-specific therapies. Harnessing induced pluripotent stem cells reprogrammed from PD patient-derived somatic cells as well as those from healthy individuals they aim to model key aspects of DA neurodegeneration. Other technologies used for study are brain organoids, stem cell transplantation and single cell sequencing to determine the reason for DA neuron degeneration. For cell replacement treatments, ‘healthy’ DA neurons will be created with gene editing from a healthy patient.
Objective
Loss of dopaminergic (DA) neurons in midbrain underlies motor dysfunction in Parkinson´s 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 PARKinson´s 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.
Fields of science
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesbasic medicineneurologyparkinson
- medical and health sciencesclinical medicinetransplantation
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
00185 Roma
Italy