*ROB HUTCHISON

A Blood-Brain Barrier Carrier Platform for Delivery of Multiple Classes of Therapeutics for Treating CNS Diseases

Challenge: The blood-brain barrier (BBB) plays an essential role in protecting the brain from blood-borne diseases. However, it blocks otherwise effective medicine from reaching the brain. Most drugs developed for treatment of central nervous system diseases fail because they aren’t optimally designed to cross the BBB. There is a need to identify natural transporters acting as ‘shuttles’ that can facilitate the transport of therapeutic cargo attached to their ligand (molecular Trojan horse) into the brain.

Solution: By screening thousands of antibodies, the team has isolated several candidates that could efficiently cross the BBB. These human single-domain antibodies were brain selective and modular and could deliver multiple classes of therapeutics, including biologics, across the BBB. Researchers then developed “fusion” molecules consisting of the BBB-crossing antibodies and therapeutic cargo molecules. The efficacy of these “fusion” molecules in treating brain diseases such as brain tumors was tested in preclinical models using novel non-invasive imaging PET scans.

Achievements/Impact: Lead antibodies were shown to deliver analgesic peptide cargos across the BBB, and to suppress pain in experimental animals after systemic administration. The identified antibodies are thus expanding the spectrum of BBB carriers that can be used for drug delivery into the brain. Moreover, they possess an improved selectivity and efficiency profile, thus demonstrating significant advantages over current delivery modalities. This innovative platform is providing the opportunity to use human BBB carriers in conjunction with a large variety of therapeutics or experimental molecules to assess efficacy in pre-clinical studies. The National Research Council of Canada will continue to characterize the BBB-crossing antibodies identified during this project, while IR&T Inc., a small company developing high-resolution PET scanners for preclinical brain imaging, will include the novel non-invasive imaging methods in their scanners.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigators:

Rob Hutchison,
Mark Day
biOasis Technologies Inc

Co-investigators

Danica Stanimirovic
National Research Council
of Canada

Reinhard Gabathuler
biOasis Technologies Inc.

Brigitte Guérin,
Roger Lecomte,
David Fortin

Université de Sherbrooke

Completed Project
$ 2,268,900 / 3 years
Supported by CQDM through:
• Merck
• Pfizer
• MEI
• BL-NCE
 
And by co-funding partners:
• National Research Council of Canada
• Brain Canada Foundation