Grant: Project Grant

GRIN disorder is a rare but debilitating genetic condition caused by disease-causing changes in the GRIN genes. These genes encode an essential neurotransmitter receptor called the NMDA receptor, which is found throughout the brain and required for proper neuronal connectivity and communication. Children with GRIN disorder experience problems from birth including low muscle tone, problems with feeding and digestion, developmental delays, profound intellectual disability, seizures, autism, visual impairment, and sleep disturbance. They will require 24-hour care for their lifetime, which is shortened by seizures, pneumonia, or cardiac arrest. There are no treatments for GRIN disorder beyond symptom management, which is often unsuccessful. We propose to develop gene therapies that could be given to both children and adults living with GRIN disorder. We are testing the ability of modified mRNA/LNP formulations to improve the molecular, cellular, and behavioural effects of GRIN disorder using mice that carry disease-causing variants in the GRIN1 gene. We will test the variables of lipid formulation, route of administration, and age of administration for outcomes of distribution, efficacy, and toxicity.