LNP-mRNA as a treatment for neurological dysfunction 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 challenge due to the protective blood brain barrier that shields the brain from the rest of the body – including therapeutics. This collaborative research project between the MacVicar Lab (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. Andrews’ project is to engineer next-generation mRNA therapeutics using human-derived stem cell ‘neurosphere’ culture systems to screen for sequences with optimal protein production, durability, and causing minimal inflammation. His work aims to generate a suite of LNP-mRNA candidate therapies to produce the vital enzyme GBA1 in the brain, which is a key target in the rare disorder neuronopathic Gaucher Disease, but also Parkinson’s Disease. This work will lay the crucial foundation for LNP-mRNA as a new drug class to treat patients with untreated brain disorders.

Dr. Daniel Andrews is a postdoctoral research fellow in the MacVicar Lab at the University of British Columbia Djavad Mowafaghian Centre for Brain Health. His 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, brain disorders, neurodegeneration, Gaucher Disease, Parkinson’s Disease