Project description
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.
Fields of science
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesbasic medicinepharmacology and pharmacypharmacokinetics
- natural sciencesmathematicsapplied mathematicsmathematical model
Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
OX1 2JD Oxford
United Kingdom
See on map
Participants (27)
751 05 Uppsala
See on map
1081 HV Amsterdam
See on map
DD1 4HN Dundee
See on map
2333 ZA Leiden
See on map
1165 Kobenhavn
See on map
8000 Aarhus C
See on map
55131 Mainz
See on map
69117 Heidelberg
See on map
1210 Wien
See on map
2342 DH Oegstgeest
See on map
The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
MK7 6AA Milton Keynes
See on map
97080 Wurzburg
See on map
30559 Hannover
See on map
2629 JD Delft
See on map
The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
53175 Bonn
See on map
The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
S10 2TN Sheffield
See on map
41121 Modena
See on map
6726 Szeged
See on map
The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
CF24 0DE Cardiff
See on map
94250 GENTILLY
See on map
CT13 9NJ Sandwich
See on map
4056 Basel
See on map
2880 Bagsvaerd
See on map
53711 Madison Wi
See on map
2340 Beerse
See on map
2500 Valby
See on map
1090 Wien
See on map