Engineering the immune response in Parkinson’s disease to curb its pathological progression
| Title | Engineering the immune response in Parkinson’s disease to curb its pathological progression |
|---|---|
| Acronym | CARgiver |
| Start date | 2026-01-01 |
| End date | 2030-12-31 |
| Sponsor | European Research Council - Advanced Grant (ERC-AdG) |
| Institution | Consiglio Nazionale delle Ricerche (CNR) |
Associated cell lines
Project Description
Mounting evidence has defined the key role played by the immune system in exacerbating dopaminergic neuron loss in Parkinson’s disease (PD). Pathological alpha-Synuclein (αSYN) activates microglia and recruits inflamed T cells, creating a toxic environment that directly negatively impact on neurodegenerative processes. Blocking or attenuating neuroinflammation can have a strong therapeutic potential in PD, but systemic treatments are associated with immune system general suppression leading to severe and unacceptable side effects. Therefore, a therapeutic strategy for long-term and local immune suppression would minimize adverse effects and provide a long-sought disease-modifying treatment for PD. To achieve this goal, we will generate innovative all-human neuroimmune organoids assembling patient and isogenic iPSC-derived neural, astroglial and microglial cells together with freshly isolated T cells. This model will recapitulate human-specific neuroinflammatory processes and assess the mechanisms regulating the interplay between neural and immune cells. This study will elucidate the role played by the immune system in fueling the neurodegenerative process and identify pathophysiological targets for the development of novel therapeutic strategies.