Mechanistic Studies of Metabolite-Signaling Defects Causing Seizures
Project Overview
Our research program is centered on investigating the important contributions of metabolism to brain health. It is generally well-accepted that proper nutrition is a major “environmental factor” that is essential for good health, yet the underlying molecular mechanisms that contribute to health are poorly understood, particularly within the central nervous system. Our research is founded on new and emerging evidence that specific metabolites called amino acids have important biochemical functions that influence brain activities by controlling communication pathways within cells. Recently, genomic sequencing studies of people with epilepsy and autism spectrum disorder have identified multiple genetic mutations in the cellular amino acid-signaling complex called GATOR1 in ~11% of individuals with familial forms of epilepsy, autism spectrum disorders, as well as people who have died from SUDEP (sudden unexpected death in epilepsy). Research has shown that the cellular activity of GATOR1 is controlled by specific dietary, amino acids, supporting a novel link between dietary amino acid composition and brain health that we aim to investigate. Our research will have a significant impact on the 20-40% of the 360,000 Canadians who are resistant to first-line epilepsy medications and will help guide nutritional strategies to block or limit seizures in people with ASD, which currently effect 1 in 66 Canadian children and youth (age 5-17), a 3-fold increase in the last 20 years. Research advancements from our program will provide a deeper understanding of the metabolic and cellular mechanisms contributing to epilepsy and ASD-linked seizures, which we aim to disseminate to neuroscience researchers and the public through community outreach programs, local and international scientific conferences, and scientific publications.
Principal Investigator
Paul Dutchak , Université Laval
Partners and Donors
Arrell Family Foundation