Dear all,

The Neurosciences axis invites you to the conference of Dr. Robert Thorne, Denali Therapeutics / University of Minnesota, Thursday, January 23 at 11 a.m. 

The conference is offered in a hybrid format, in person at the CHUL, amphitheater Fisher and broadcast on zoom (https://us02web.zoom.us/j/89120656487).

Here is the title and summary of the presentation:

Title : Leveraging physiology and engineering for CNS drug delivery: transporting antibodies and enzymes to the final frontier.

Abstract : Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB), a key border separating the general blood circulation from the brain parenchyma (Badaut et al. Fluids & Barriers of the CNS, 2024). We have developed novel BBB transport vehicles (TVs) comprising engineered Fc fragments that exploit transcytotic pathways across brain endothelial cells for the CNS delivery of biotherapeutics. TVs have been engineered using directed evolution to bind either the apical domain of the human transferrin receptor (Kariolis et al. Science Translational Medicine, 2020) or CD98 heavy chain (Chew et al. Nature Communications, 2023), two highly expressed brain endothelial cell targets. Results will be presented demonstrating how these transport vehicle approaches may be paired with a variety of different payloads (e.g. antibodies, enzymes, and antisense oligonucleotides) for increased brain exposures and therapeutic effects in animal models and in human beings. Our work suggests this modular TV platform approach has great potential for the CNS delivery of multiple protein therapeutics covering a range of neurological disorders including Alzheimer’s disease, brain cancers, and neuronopathic mucopolysaccharidoses.