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Drug DELIvery to the brain via CHOroid Plexus targeting

Project description

Central nervous system therapy through choroid plexus targeting

Central nervous system (CNS) disorders, such as brain cancer and Alzheimer’s disease, are difficult to treat, with CNS medications generally having lower success rates compared to non-CNS drugs. This is mainly due to barriers like the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier, which limit drug delivery to the brain. The ERC-funded DeliChoP project will explore targeting the choroid plexus (ChP) at the blood-CSF barrier as a novel strategy for delivering therapeutics. The project aims to identify substances that can effectively reach specific brain regions and evaluate additional receptor-mediated transport (RMT) targets. This research could position the blood-CSF barrier as a promising pathway for developing new CNS therapies.

Objective

CNS disorders, e.g. brain cancer and Alzheimers disease, are the most common, debilitating, and underserved diseases. CNS drugs have historically suffered from considerably lower success rates during development than those for non-CNS indications. One of the major reasons is the presence of CNS barriers, including the blood-brain (BBB) and blood-cerebrospinal fluid (CSF) barrier. These blood-brain interfaces severely restrict the cerebral bioavailability of pharmaceutical compounds. While numerous attempts have been done to find methods to efficiently shuttle compounds over the BBB, less work has been done on blood-CSF crossers.
Here, I hypothesize that targeting the blood-CSF barrier at the choroid plexus (ChP) is an attractive, innovative and underexplored strategy to deliver therapeutics to the brain. Indeed, this CNS barrier forms a unique interface between blood and CSF and delivery of therapeutics across the ChP epithelial cells may offer added-value for the treatment of CNS diseases. Recently, we could show that the blood-CSF barrier, via hijacking the FOLR1 pathway, is indeed a novel and exciting entry site to deliver therapeutics to the brain. Proof of concept data convincingly show that our in house generated anti-FOLR1 single domain antibody (VHH) is able to deliver a peptide into the brain. Undoubtfully, further validating the use of this VHH as brain shuttle could have major therapeutic implications. Here, I aim to investigate: (1) which cargos can be shuttled into (specific regions of) the brain, (2) which neurological disorders might be targeted and (3) whether other RMT targets at the blood-CSF barrier have similar brain targeting capacity.
This project will finally reveal whether the blood-CSF barrier is an interesting entry route to the brain with therapeutic potential. Consequently, I infer that the data generated from this project may provide major impetus to the development of novel therapeutic strategies for the treatment of CNS diseases.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

VIB VZW
Net EU contribution

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.

€ 1 999 756,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost

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.

€ 1 999 756,00

Beneficiaries (1)

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