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, NRC-HHT 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.
- Non-exclusive commercial exploitation licence
- R&D agreement for development
- 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
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.
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, NRC-HHT'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 NRC-HHT 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.
- 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
- NRC file 11085 (1st generation receptors): Patent issued in Canada, the United States, and Europe.
- NRC file 11750 (1st generation sdAbs): Patent issued in Japan, pending in Canada, the United States, Europe and India.
- NRC file 12133 (analgesic, anti-epileptic neuropeptide): Patents pending in Canada, the United States and Europe.
- NRC file 12596, 12599, 12600 (2nd generation receptors and sdAbs): Provisional patents filed in the United States.