In vivo testing of LNP-mRNA therapeutics in an animal model of Gaucher Disease

Severe brain disorders are the second leading cause of death and leading cause of disability worldwide. Drug development for these disorders has remained a significant hurdle due to the protective blood brain barrier that shields the brain from the rest of the body – including therapeutics. This collaborative research project between Dr. Brian MacVicar (UBC) and CereCura Nanotherapeutics is focused on a solution to this longstanding problem, using a novel technology that empowers the brain to manufacture its own medicines inside the brain compartment. This approach builds upon the lipid nanoparticle (LNP) and messenger RNA (mRNA) technologies that were used in the COVID vaccines to enable long-term, stable production of protein-based therapeutics to treat brain disease. Dr. Radisavjevic’s project is to establish LNP-mRNA as a viable strategy in the brain as a therapeutic for neuronopathic Gaucher Disease, a rare and fatal disorder that is completely untreated. Neuronopathic Gaucher Disease is caused by dysfunction in the vital enzyme GBA1. Using state of the art LNP-mRNA candidate therapies generated by our group, she will assess whether LNP-mRNA to supplement GBA1 protein can restore enzyme activity and reverse neurological manifestations of the disorder. This study will establish a key therapeutic proof of concept for the LNP-mRNA platform as a whole, by examining the pharmacology, safety, and efficacy of these novel medicines.

Dr. Radisavljevic is a postdoctoral research fellow in the MacVicar Lab at the University of British Columbia Djavad Mowafaghian Centre for Brain Health. Her internship is jointly funded by Michael Smith Health Research BC, Mitacs, and CereCura Nanotherapeutics, through the “Health Research BC-Mitacs Industry-Based Opportunity” partnered funding program.

Keywords: lipid nanoparticle (LNP), messenger RNA (mRNA), therapeutics, platform technology, in vitro, stem cells, brain disorders, neurodegeneration, Gaucher Disease, Parkinson’s Disease