Abstract:
Efficient transcytosis across the blood-brain-barrier (BBB) is an important strategy for accessing drug targets within the central nervous system (CNS). Despite extensive research the number of studies reporting successful delivery of macromolecules or macromolecular complexes to the CNS has remained very low. In order to expand current research it is important to know which receptors are selective and abundant on the BBB so that novel CNS-targeting antibodies or other ligands could be developed, targeting those receptors for transcytosis. To do that, we have set up a proteomics- and transcriptomics-based workflow within the COMPACT project (Collaboration on the Optimization of Macromolecular Pharmaceutical Access to Cellular Targets) of the Innovative Medicines Initiative (IMI) of the EU. Here we summarise our overall strategy in endothelial transcytosis research, describe in detail the related challenges, and discuss future perspectives of these studies.
Keywords
Blood-brain-barrier; Transcytosis; Proteomics; Next generation; Sequencing; Drug delivery
Citation: Imre Mager, Axel H. Meyer, Jinghuan Li, Martin Lenter, Tobias Hildebrandt, German Leparc, Matthew J.A. Wood.Targeting Blood-brain-barrier Transcytosis-Perspectives For Drug Delivery http://dx.doi.org/10.1016/j.neuropharm.2016.08.025
Received: 20 January 2016, Revised: 18 June 2016, Accepted: 19 August 2016, Available online: 22 August 2016
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Acknowledgements
This work has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115363 resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies' in kind contribution.