Grant: Project Grant

Tuberous sclerosis complex (TSC) is a genetic disease that affects the brain. TSC can lead to the development of epilepsy and intellectual disability, as well as tumours cerebral tubers (form of hamartoma). TSC affects the molecular pathway in the body that, amongst other functions, is important for controlling the human immune system, referred to as the mTOR pathway. We hypothesize that combining advanced genetics and brain imaging with blood biomarkers of brain inflammation/injury will identify children with TSC at risk of developing severe brain disease, as well as how this may change as they age, and predict their response to TSC-specific therapies. This proposal will extend our already-underway CaTS cohort (100+ adults/adolescents with TSC) by recruiting 120 children from 3 of the largest TSC clinics for children in Canada (CaTS-peds). We will combine advanced genetic testing and brain imaging (magnetic resonance imaging) with an extensive list of blood tests that are associated with brain and blood inflammation and injury. We will examine the pattern of these molecular and imaging biomarkers in different TSC groups and how they can predict the future severity of epilepsy as well as intellectual disability. We will study how these can predict a child's response to therapies that act on the mTOR pathway (mTOR inhibitors). It remains only partially understood why some people with TSC have severe brain disorders while others do not. Our proposal will provide a better understanding of how advanced genetics and brain imaging combined with blood markers of brain inflammation and injury are associated with brain disorders in people with TSC. This better understanding would allow doctors to identify brain disorders before they become physically evident. It would also allow for the better prediction of long-term outcomes in people with TSC and the better selection of individuals to treat with TSC-specific therapies such as mTOR inhibitors.