Project description
Electrical spinal cord stimulation for Parkinson’s disease
Parkinson’s disease is a progressive neurodegenerative disorder that is associated with tremors, rigidity and loss of balance. Nearly half of the patients suffer from low blood pressure upon standing which causes falls, fatigue and stroke. A promising neurosurgical approach uses epidural electrical stimulation of the spinal cord to prevent these episodes, with encouraging early results. The ERC-funded HemoPARK project aims to investigate the mechanisms by which electrical stimulation engages the nervous system in Parkinson’s disease. To achieve this, the research team will combine single-cell sequencing, optogenetics and gene editing in rodent models. Findings will advance understanding of how neurodegeneration reorganises neural circuits and how electrical stimulation can restore lost neurological functions.
Objective
About 1 million people with Parkinson’s disease live in the EU, including those with atypical parkinsonian syndromes. Up to 50% of them suffer from severe hypotensive symptoms, which include debilitating episodes of fatigue, nausea, and syncope. These complications are a significant cause of morbidity as they decrease mobility, increase the incidence of falls, reduce quality of life, and increase the risk of stroke. We recently developed a neurosurgical approach that applies epidural electrical stimulation (EES) over the thoracic spinal cord to prevent hypotension in people with spinal cord injury, and also demonstrated proof of concept in one patient with multiple system atrophy. While these results encouraged us to implant a second patient with multiple system atrophy, we found that the effect of EES on orthostatic hypotension was considerably less effective. This observation suggested that improper patient selection could render the therapy ineffective, and that the mechanisms underlying pressor responses induced by EES in parkinsonian syndromes may differ from those in people with spinal cord injury. Here, we will conduct a series of mechanistic experiments in newly developed rodent models of parkinsonian syndromes to understand how EES accesses sympathetic circuits in neurodegenerative states, and how long-term EES impacts these circuits. To address these questions we will deploy a combination of single-cell RNA sequencing, optogenetics, and CRISPR-Cas9 knockouts. Finally, we will leverage the mechanistic insight gained from these experiments to carefully select two participants who will be implanted with EES to treat severe orthostatic hypotension. The proposed work will expose fundamental mechanisms by which neurodegeneration provokes circuit reorganisation, how neuromodulation therapies can leverage this reorganisation to gain access to the circuits required to restore neurological functions, and use this understanding to develop new therapies.
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
- medical and health sciences basic medicine neurology stroke
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine neurology parkinson
- medical and health sciences medical biotechnology implants
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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.1.1 - European Research Council (ERC)
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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.
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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-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2025-STG
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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.
1011 Lausanne
Switzerland
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