Project description
Novel mediators of Huntington’s disease
Huntington’s disease is a fatal inherited neurodegenerative disorder affecting tens of thousands of people across Europe. Currently, there is no effective treatment capable of halting or slowing disease progression, while existing biomarkers fail to detect early pathological changes. With the support of the Marie Skłodowska-Curie Actions programme, the AstroExo-HD project investigates a novel astrocyte-driven mechanism underlying Huntington’s disease. The working hypothesis is that these glial cells release abnormal extracellular vesicles that contribute to neuronal damage. Using patient-derived cell models, researchers will analyse the molecular composition of extracellular vesicles and identify cargo molecules that could serve as early biomarkers or therapeutic targets for Huntington’s disease and related neurodegenerative disorders.
Objective
Huntington’s Disease (HD) is a fatal neurodegenerative disorder affecting 10-13/100,000 across Europe, with an annual economic burden of €3B+. No therapy halts or delays progression. Existing interventions such as antisense oligonucleotides are of limited efficacy, while current biomarkers (neurofilament light chain, mutant huntingtin in CSF, neuroimaging) either detect late-stage damage, lack cell-type specificity or require invasive sampling.
This fellowship will investigate a novel mechanistic axis proposing that astrocytic proteostasis failure leads to altered extracellular vesicle (EV) signalling that contributes to neuronal dysfunction. The project leverages directly reprogrammed patient fibroblasts into astrocytes and neurons that retain transcriptomic and epigenetic signatures of aging, providing a uniquely relevant model of late-onset HD.
The interdisciplinary approach integrates multi-omics profiling (proteomics, RNA-seq), bioinformatics-driven prioritisation, functional testing in patient-derived neurons and mechanistic validation of both toxic gain- and loss-of-function EV cargoes to define novel avenues for effective treatment identification. This design adds mechanistic depth often missing in current biomarker studies and ensures robustness across discovery, validation and translation.
Expected outcomes include high-quality datasets, prioritized cargo candidates and functional assays adaptable to other neurodegenerative diseases (ALS, FTD, AD). These results will support the development of next-generation biomarkers (ADEVs measurable in biofluids) and lay the foundation for therapeutic strategies, such as nanobody-based neutralisation, while such development beyond the PF timeframe.
Through targeted dissemination, IP protection, and intersectoral training this fellowship will strengthen EU’s role in precision neurodegeneration, while equipping me with advanced expertise, leadership skills, a broad professional network and a platform for independence.
Fields of science (EuroSciVoc)
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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 biochemistry biomolecules proteins proteomics
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
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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-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-2025-PF
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54 066 Wrocaw
Poland
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