Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Mechanism-driven neuroprosthetics to restore hemodynamic stability in parkinsonian syndromes

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)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

See all projects funded under this funding scheme

Call for proposal

(opens in new window) ERC-2025-STG

See all projects funded under this call

Host institution

CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS
Net EU contribution
€ 1 500 000,00
Address
RUE DU BUGNON 21
1011 Lausanne
Switzerland
Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 500 000,00

Beneficiaries (1)