Several challenges have yet to be addressed to better understand the role and alterations of the Blood Brain Barrier (BBB) and transport mechanisms in health and diseases. This is particularly critical for neurodegenerative diseases (e.g. Alzheimer and Parkinson’s diseases, Amyotrophic Lateral Sclerosis (ALS)), vascular dementia, multiple sclerosis and metabolism-related central diseases (diabetes and obesity). It will be also important to understand the mechanisms of neurotropic virus-mediated BBB and brain penetration, and to be able to apply this knowledge for the development of innovative drug delivery systems, especially for biopharmaceuticals, and the identification of novel drug targets. Furthermore the various transport mechanisms and potential drug delivery systems that have been suggested so far need validation by independent researchers and the further understanding of challenges to advancing into clinical drug development by biotech/pharma.
The objectives of the project to be delivered from this topic are:
These objectives could be attained through the milestones shown hereunder. Each of them could represent an independent work package and will be described later in the topic text:
The use of ‘healthy’ and patient-derived specimens, inducible pluripotent stem cell (iPSC) clones and other types of progenitors offers compelling approaches due to the direct connection to patients with the underlying disease. The impacts of these new models could include: (1) yielding novel insights into currently identified BBB transport mechanisms for drugs, especially biopharmaceuticals, (2) allowing to use comparative assessment between ‘healthy’ and ‘diseased’ BBB, including in silico models, to prioritise some approaches for specific disease(s) because the transport mechanism is modified in the disease state, (3) leading to the identification and characterisation of novel transport mechanisms that are unaffected or upregulated in the disease or neurotropic virus-mediated, making them even more interesting, and (4) facilitating the discovery and characterisation of novel targets addressing the vascular aspect of neurological disorders like AD and thus open up novel routes for therapy.