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

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 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.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2021-PF-01

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Coordinator

CONSIGLIO NAZIONALE DELLE RICERCHE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 188 590,08
Address
PIAZZALE ALDO MORO 7
00185 Roma
Italy

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Region
Centro (IT) Lazio Roma
Activity type
Research Organisations
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Total cost

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