MAR 14, 2018 6:00 AM PDT

Targeting the Blood-Brain Barrier Transferrin Receptor for Delivery of Biologics for Alzheimer's Disease

Presented at: Neuroscience 2018
Speaker
  • Assistant Professor of Biopharmaceutical Sciences, Keck Graduate Institute School of Pharmacy
    Biography
      Dr. Sumbria received a Bachelor of Technology (B.Tech) in Pharmaceuticals & Fine Chemicals from the Institute of Chemical Technology in Mumbai, India in 2005, and a PhD in Pharmaceutical Sciences from the Texas Tech University Health Sciences Center (TTUHSC) in 2010. At TTUHSC, her research centered on the development of intracerebral microdialysis as an experimental tool to study changes in the blood-brain barrier (BBB) permeability in ischemic stroke. Dr. Sumbria completed her postdoctoral training at the Department of Medicine, blood-brain barrier laboratory at the University of California, Los Angeles and the Department of Neurology at the University of California, Irvine from 2011-2014. During her postdoctoral research at UCLA, Dr. Sumbria focused on the problem of the BBB bottleneck in CNS drug delivery. Particularly, her research focused on the use of receptor-mediated transcytosis for non-invasive delivery of biologics across the BBB, and studying their pharmacologic effects in different experimental models of CNS disorders. At UCI, the focus of her research was studying the role of cerebral microbleeds in cerebrovascular diseases like stroke. She joined the Keck Graduate Institute School of Pharmacy as an Assistant Professor in 2014 and is extensively involved in teaching and blood-brain barrier research. Her research is funded by the Alzheimer's Association, Joseph H. Stahlberg Foundation and NIH.

    Abstract

    98% of small molecules and 100% of large molecules do not cross the blood-brain barrier (BBB). Biologics, including therapeutic antibodies (e.g. anti-amyloid antibodies), have been at the forefront of Alzheimer’s disease (AD) research, however have had limited success so far. Biologics are large molecules with limited permeability across the BBB, and in the absence of a BBB-targeting approach to deliver these biologics to the brain, the true potential of the biologic cannot be determined. One approach to deliver a biologic, including anti-amyloid antibodies, decoy receptors and neurotrophins, for AD is to engineer bispecific fusion proteins, such that one domain of the fusion protein is the therapeutic biologic of interest, and the other domain acts as a molecular Trojan horse to ferry the biologic into the brain. This talk will focus on some of our work involving the targeting of the BBB transferrin receptor to deliver biologics (e.g. anti-amyloid antibody and biologic TNF-a inhibitor) in mouse models of AD.


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