Project description
Targeted immunotherapy for Parkinson’s disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the accumulation of alpha synuclein, a protein that regulates synaptic vesicle trafficking and neurotransmitter release. Abnormal forms of alpha synuclein activate immune cells in the brain, causing neuroinflammation and accelerating neurodegeneration. The ERC-funded CARgiver project aims to develop a novel targeted therapy using chimeric antigen receptor (CAR) regulatory T cells (Tregs) that suppress immune activation only where pathological alpha synuclein is present. Researchers will test the efficacy of these CAR Tregs in mouse and humanised PD models. Additionally, they will engineer CAR Tregs to locally prevent alpha synuclein aggregation, offering a disease-modifying treatment that may be applied across all PD stages.
Objective
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 have generated αSYN-specific CAR T regulatory cells (Tregs) that are activated and recruited only in the presence of toxic αSYN aggregates, suppressing immune activation. Herein, we will determine the therapeutic efficacy of mouse and human αSYN-CAR Tregs in conventional and humanized mice with virally-induced synucleinopathy. These experiments will determine the dose and infusion schedule that will achieve maximal neuroprotection and symptomatic rescue with none or minimal side effects. Moreover, innovative all-human neuroimmune organoids will be generated by assembling patient and isogenic iPSC-derived neural, astroglial and microglial cells together with freshly isolated T cells and αSYN-CAR Tregs. This model will recapitulate human-specific neuroinflammatory processes and validate the capacity of αSYN-CAR Tregs to interfere with them. Finally, we conceived αSYN-CAR Tregs as ideal cellular shuttles for the local delivery of therapeutic molecules and this concept will be explore to express αSYN anti-aggregating agents. This treatment is of potential benefit for the entire PD patient population at any given stage of the disease and pharmacological regimen, and with a straightforward clinical implementation path using an autologous cellular source.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-ADG
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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.
00185 Roma
Italy
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