Project description
A sound approach to slowing Parkinson’s dementia
More than half of patients diagnosed with Parkinson’s disease develop dementia as the condition progresses. This cognitive decline is linked to toxic protein aggregates in the brain and impaired microglial activity (the cells responsible for clearing such waste). The EU-funded FUMA project will investigate whether focused ultrasound with microbubbles can help. This non-invasive technique temporarily opens the blood–brain barrier, allowing the brain to clear harmful proteins and restore synaptic health. In mouse models of Parkinson’s dementia, FUMA will test whether this method improves cognition and slows neurodegeneration, while also identifying imaging biomarkers and molecular pathways. If successful, it could lay the groundwork for a new, safer therapy for Parkinson’s-related dementia.
Objective
Over half of Parkinson Disease patients develop cortical dysfunctions leading to Parkinson Disease Dementia (PDD). The cognitive changes are primarily driven by pathological alpha-synuclein (a-syn) protein aggregates with secondary synaptic dysfunctions in the cortex. Microglia plays a key role in synapse maintenance and clearance of aggregated a-syn proteins, however, this is impaired in PD.
Low intensity focused ultrasound (FUS) combined with intravenous microbubbles (MB) can non-invasively increase the permeability of the blood-brain barrier, resulting in a transient and controlled entry of blood-born substances. In animal models of Alzheimer disease, FUS-MB treatments increase microglial-mediated clearance of extra- and intracellular protein aggregates and improve synapse health. In small patient cohorts in the clinic, FUS-MB treatments are safe and results suggest decreased levels of pathological proteins in Alzheimer disease patients.
HYPOTHESIS: FUS-MB applications targeted to the cortex promote cortical a-syn clearance and synapse maintenance which can prevent or slow the development of dementia in PD.
In a mouse model of PDD we will determine the ability of FUS-MB treatment to increase microglial-mediated clearance of a-syn, maintain synapse health, and inhibit the development of cognitive dysfunctions. In addition, we aim to evaluate non-invasive positron emission tomography and magnetic resonance imaging as biomarkers of the effects of FUS-MB treatment. Finally, we will investigate the underlying pathway of potentially beneficial effects of FUS-MB treatments by measuring changes in specific pathways of interest as well as perform an unbiased screen for novel targets.
Both the researcher and supervisor have a background in Parkinson disease research. The researcher brings expertise in FUS-MB treatments of mouse models and the supervisor is an expert in preclinical and clinical neuromodulation, the latter with FUS.
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.
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology neurodegenerative diseases parkinson
- natural sciences physical sciences acoustics ultrasound
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2022-PF-01
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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.
8000 Aarhus C
Denmark
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.