Principal Investigator
Sébastien Tremblay
Université Laval – CERVO
Co-investigator
Brian MacVicar
University of British Columbia
Project of $1,464,765 over 3 years
- Supported by CQDM through:
Ministère de l’Économie, de l’Innovation et de l’Énergie du Québec (MEIE) - And by co-funding partners:
– RNA Technologies & Therapeutics (RNA T&T)
– CereCura Nanotherapeutics
– Brain Canada Foundation
Challenge
Delivery of therapeutic proteins to the brain has been a longstanding barrier to Central Nervous System (CNS) drug development. Protein replacement or supplementation strategies hold promise for multiple brain diseases, from enzyme-replacement for neuronopathic lysosomal disorders, to growth factor supplementation for neurodegeneration, to cytokine immunotherapy for brain cancers. However, most brain diseases remain poorly treated in part due to the inability to deliver proteins to the brain with a disease-appropriate biodistribution.
Solution
Prof. Sébastien Tremblay’s team (Université Laval-CERVO), in collaboration with Prof. Brian MacVicar’s team (University of British Columbia; UBC) will address the brain protein delivery challenge using lipid nanoparticle (LNP) to bring to brain cells the RNAm blueprint that encodes for a therapeutic protein. LNP-RNAm products instruct the host cell to secrete a desired protein that then diffuses broadly throughout the brain, effectively harnessing brain cells to become ‘protein factories’ within the brain itself.
Expected Achievements/Impact:
The co-funders CereCura Nanotherapeutics Inc. and RNA Technologies and Therapeutics Inc. have shown the strategy is viable in rodents, demonstrating this versatile technology can deliver multiple proteins with unprecedented spatiotemporal distribution in the brain. Leveraging the expertise of Prof. Sébastien Tremblay and his Translational Neurosurgery Laboratory in optimizing genetic drug delivery to non-human primate (NHP) brains and that of Prof Brian MacVicar at UBC in mouse models of neurological diseases, this multidisciplinary team will 1) demonstrate the feasibility of LNP-RNA-induced protein delivery to NHP brain, 2) optimize the RNA cargo of a lead candidate drug product using in vitro models and 3) validate its therapeutic in a specific disease use case (neuronopathic lysosomal disease).
Moreover, the combination of Montreal-based company RNA technologies and Therapeutics’ expertise in RNA sequence design and optimization, high-quality RNA synthesis (preclinical and clinical), lipid formulation development and LNP surface modification for specific targeting, with the expertise of Vancouver LNP development hub, will bring us one step closer to first-in-human trials, bringing hope to Quebecers and Canadians suffering from debilitating brain diseases.
