Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics...
Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics IM2PACT Into The Brain
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 ide...
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Información proyecto IM2PACT
Duración del proyecto: 72 meses
Fecha Inicio: 2018-12-14
Fecha Fin: 2024-12-31
Descripción del proyecto
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.