Highlights
The blood brain barrier (BBB) is the principal hurdle in developing drugs for central nervous system (CNS) diseases such as Alzheimer's, Parkinson's, brain cancer, epilepsy, and others. Composed of tightly adjoined endothelial cells, the BBB actively repels foreign matter from the brain; virtually no biologic molecules are able to cross it to elicit a therapeutic response.
To address the need for disease-modifying CNS biologics, the NRC has developed carriers for delivering therapeutics beyond brain barriers. They can be coupled to a wide range of client molecules in order to prevent, diagnose, and treat CNS diseases.
Technology transfer
- Non-exclusive commercial exploitation licence
- R&D agreement for development
Market applications
- Deliver therapeutic antibodies, peptides, enzymes and proteins across the BBB for prevention and treatment of neurodegenerative and other CNS diseases
- Deliver contrast agents across the BBB for diagnostic / prognostic imaging
- Deliver nanoparticles carrying therapeutics across the BBB
How it works
The NRC's BBB carriers are single-domain antibodies (sdAbs) that bind to BBB-expressed receptors, internalize into BBB cells and transmigrate across the BBB into the brain. The technology exploits a process known as receptor-mediated transcytosis (RMT) across the BBB, which is amenable for delivery of both small molecular weight therapeutics and biologics including peptides, antibodies and RNA.
Various configurations of sdAbs used as BBB carriers: (1) with imaging probes; (2) as fusion proteins with other sdAbs, peptides, growth factors, and monoclonal antibodies; (3) as immunoconjugates with enzymes and nanocarriers.
In contrast to competing RMT BBB delivery technologies that use the transferrin, insulin, or LRP1/2 receptor(s) expressed at the BBB to carry molecules into the brain, the NRC's technology utilizes novel, recently discovered receptors involved in BBB RMT. Unlike other receptors listed above, which are highly expressed in peripheral organs and therefore lack selectivity, the receptors exploited by the NRC are enriched in the blood-brain barrier and up-regulated in specific brain diseases. This enables carrier-coupled therapeutics to target the brain with higher selectivity.
Benefits
- Two generations of sdAbs that are small (13 kD), stable, humanized, and easily customizable
- sdAbs target novel, highly selective receptors
- Preclinical proof of concept established in vivo
Patents
- NRC file 11085 (1st generation receptors): Patent issued in Canada, the United States, and Europe.
- NRC file 11750 (1st generation sdAbs): Patented in Canada.
- NRC file 12133 (analgesic, anti-epileptic neuropeptide): Patented in Canada, the United States, and Europe.
- NRC file 12596, 12599, 12600 (2nd generation receptors and sdAbs): Patents filed in several countries globally, including Canada, the United States, Europe, Japan, and China.
- NRC file 2017-006 (2nd generation receptors): Patents filed in several countries globally, including Canada, the United States, Europe, Japan, and China.
Related links
Contact us
Stacey Nunes, Director, Business Development
Telephone: 613-993-9212
Email: Stacey.Nunes@nrc-cnrc.gc.ca