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Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics (IM2PACT) Into The Brain

Project description

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The blood–brain barrier and delivery of biopharmaceuticals to the brain

The overall goal of the EU-funded IM2PACT project is to further our understanding of the blood–brain barrier (BBB) in health and disease in order to develop innovative systems for the delivery of biopharmaceuticals to the brain and identify novel drug targets for Alzheimer’s disease, multiple sclerosis and metabolic disease. Researchers will identify specific genes altered in brain endothelial cells in disease and establish new disease genetic models followed by the generation and characterisation of robust and predictive stem cell-derived BBB models. Next, they aim to develop efficacious and safe mechanisms and technologies for brain delivery, employing neurotropic virus-mediated BBB selective penetration systems and establishing in silico models to predict BBB penetration for therapeutics and pharmacokinetics in different compartments of the neural system.

Objective

The overall aim is to further the understanding of the BBB in health and disease states towards the development of innovative brain delivery systems, especially for biopharmaceuticals (e.g. peptides, antibodies, etc.) and the identification of novel disease drug targets (Alzheimer’s Disease, MS, metabolic disease). The related key deliverables will be as follows:

1.Identification and validation of specific genes and/or mechanisms which are altered in brain endothelial cells in disease.
2. Generation, validation and characterisation of robust and predictive iPSC-derived BBB models: The developed models should be more reflective of the in vivo situation than existing models, in the healthy and disease states.
3. New, efficacious and safe mechanisms and technologies of brain delivery: The output of this topic should also result in an expanded and deepened understanding of the fundamental processes that underpin drug-trafficking across the BBB, which in turn can further support endeavours to elucidate novel and more efficacious brain delivery mechanisms.
4. Characterised new genetic models for the diseases of interest in this topic which are better amenable to evaluate disease-modifying agents.
5. Characterised mechanisms of neurotropic virus-mediated BBB and CNS penetration for development of selective brain delivery systems.
6. Established in silico/mathematical models in predicting BBB penetration of therapeutics (such as receptor-or carrier-mediated transcytosis for delivery across the BBB) and pharmacokinetics of biopharmaceutics in different compartments of CNS.
7. Identification of relevant translational readouts which are better amenable to elucidate the role of the BBB in the pathogenesis of neurodegeneration and could eventually lead to new targets for the treatment of the neurovascular causes of the diseases.

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Topic(s)

Call for proposal

H2020-JTI-IMI2-2017-12-two-stage

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Funding Scheme

RIA - Research and Innovation action

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution
€ 2 218 291,27
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 2 233 291,27

Participants (27)

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Last update: 4 November 2024

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Permalink: https://cordis.europa.eu/project/id/807015

European Union, 2024