Project description
Breaking barriers in brain drug delivery
Over 540 million people in Europe live with neurological disorders, yet treatments often fall short. This is largely because getting drugs into the brain remains a major hurdle. Supported by the Marie Skłodowska-Curie Actions programme, the SH-CNS-AM project is taking a bold, virus-inspired leap to change that. Scientists are developing a delivery system based on a protein from the mumps virus, capable of slipping therapeutic compounds through the brain’s protective barriers via the GPR125 receptor. Early tests are promising in mice, the protein linked to Exendin-4 reduced appetite, proving it works. Now, researchers will explore how these protein-drug shuttles move, how long they last, and whether they can ease pain. If successful, the method could unlock powerful new treatments for Alzheimer’s, Parkinson’s, ALS, and so on.
Objective
Neurological disorders affect over 540 million individuals in Europe alone, yet effective treatments are limited, primarily due to the challenge of delivering therapeutic compounds across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). This project aims to develop a novel, virus-inspired technology that utilizes small hydrophobic (SH) proteins, derived from the neurotropic mumps virus to shuttle CNS-active molecules across the BCSFB via the GPR125 receptor. This innovative approach will allow for the effective delivery of therapeutic agents and avoid issues surrounding chemical modification and viral vector packaging of drugs.
Building on promising preliminary data, where an SH protein conjugated to Exendin-4 significantly reduced appetite in mice, this project will focus on understanding transport mechanisms of SH-conjugated molecules into the brain. The research will be divided into three work packages (WPs). WP1 will investigate the mechanism of SH-GPR125 transport in vitro using choroid plexus cells and advanced imaging techniques. WP2 will examine the pharmacokinetics and bioavailability of SH-Silicon Rhodamine (SiR) in vivo, determining its uptake in GPR125 knockout and wild-type mice. WP3 will assess the efficacy of SH-enkephalin, a therapeutic peptide targeting the mu-opioid receptor, in an acute pain model, testing its ability to reduce pain perception in mice.
This project offers a transformative approach to CNS drug delivery, with the potential to revolutionize treatment for a range of neurological disorders, including Alzheimer’s, Parkinson’s, and ALS. By leveraging the natural ability of neurotropic viruses to cross the BCSFB, we propose a method that bypasses current limitations in CNS drug delivery. The outcomes of this research will provide a foundation for future clinical applications, potentially leading to new therapies that address the urgent unmet medical needs posed by neurological disorders.
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 microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmacokinetics
- medical and health sciences basic medicine neurology neurodegenerative diseases parkinson
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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)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-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.
1165 KOBENHAVN
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.