Identifying New Noninvasive Transendothelial Routes for Brain Drug Delivery
Abstract
The development of medical countermeasures to chemical and biological threats that affect the central nervous system (CNS) hinges on the capability to deliver such countermeasures to brain tissue. Blood-borne countermeasures such as oximes or antiviral therapeutics would encounter the blood-brain barrier (BBB), a known obstacle to the delivery of small molecule pharmaceuticals, biologics and nanomedicines. This proposal is focused on using human BBB models derived from induced pluripotent stem cells (iPSCs) to screen for antibodies capable of traversing this barrier that can potentially carry countermeasures into the brain noninvasively. Our current screening approach utilizes homogeneous monocultures of iPSC-derived brain endothelial cells for antibody identification. However, it is also becoming more apparent that the pericytes which invest and share a basement membrane with the BBB can play important roles in regulating BBB properties such as permeability and transcellular transport (e.g. Daneman et al., Nature, 2010 and Armulik et al., Nature 2010). Thus, we propose development of a robust, renewable source of human iPSC-derived brain pericytes that could be combined with our iPSC-derived brain endothelial cells to further enhance the properties of our in vitro BBB model screening and evaluation system. Moreover, iPSC-derived brain pericytes would provide an additional resource for those groups within the DTRA Advanced and Emerging Threat Division Project that are modeling the BBB to explore the penetration of various chemical and biological threats and countermeasures.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2016
- Source ID
- HDTRA11510012
Entities
People
- Eric V Shusta
Organizations
- Defense Threat Reduction Agency
- University of Wisconsin System