Objective
NeuroDegRNA-Tx aims to develop and validate a novel mRNA-based therapeutic strategy that enhances intrinsic cellular resilience to treat Alzheimer’s disease (AD). While most current treatments focus on removing the causative protein aggregates, the NeuroDegRNA-Tx approach leverages our recent discovery of a novel stress-resilience mechanism, which we named as SITA (Stress-Induced Transcriptional Attenuation). SITA enables cells to suppress non-essential transcription during the stress of protein misfolding, sparing cellular resources for preserving protein homeostasis. Our data showed that SITA deficiency accelerates disease progression in mouse models of AD. Using genome-wide CRISPR screens, we identified several SITA enhancers (SITAe) as promising therapeutic targets.
NeuroDegRNA-Tx will test whether mRNA delivery of SITAe in diseased brains can restore SITA function and reduce disease phenotypes in established mouse models of AD. Using lipid nanoparticle (LNP)-encapsulated mRNA, we will validate hippocampal delivery, assess protein expression, and evaluate behavioural improvements. Single-cell RNA sequencing will confirm target engagement and cell-type-specificity while ensuring therapeutic safety. A lead SITAe candidate will be selected based on efficacy and safety.
Commercially, the project will generate critical preclinical data to support patenting, derisk translational development and prepare for follow-up funding through schemes such as EIC Transition. Stakeholder involvement includes academic leaders in RNA therapeutics, neurodegeneration and cellular stress biology, as well as Cambridge Enterprise for IP and commercial strategy.
By combining breakthrough mechanistic insights with the enormous potential of RNA-based drugs, NeuroDegRNA-Tx will shift the treatment paradigm from elimination of protein aggregates to improvement in cellular resilience. The project will pave a novel therapeutic avenue in neurodegeneration using mRNA therapeutics.
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.
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.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- engineering and technology nanotechnology nano-materials
- medical and health sciences basic medicine physiology homeostasis
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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)
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.
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-POC - HORIZON ERC Proof of Concept 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-2025-POC
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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.
CB2 1TN CAMBRIDGE
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.