Progress in the treatment of neurological disorders has been limited by the lack of an experimental system that captures the unique biology and developmental program of the human brain. Recently, advances in human stem cell engineering have enabled the generation of human brain cells, called neurons, in a culture dish. These neurons behave remarkably like the ones in the human brain and can be genetically engineered to allow in depth mechanistic studies into the causes underlying human neurological disorders. Here we will use this state-of-the-art approach to uncover disease mechanisms for Tuberous Sclerosis Complex (TSC), a neurodevelopmental disorder associated with autism spectrum disorder and epilepsy. TSC is caused by mutations in the TSC1 or TSC2 genes, which help regulate cell growth and division. TSC causes benign tumours to form throughout the body, as well as focal brain malformations called "tubers", which are often the sites of seizure generation. By gene-editing stem cells to create mutations in TSC1 or 2, we can control the precise time when the mutation occurs, allowing us to characterize how the mutations impact the early steps of human brain development. In addition to gene-editing normal stem cells, it is possible to create stem cells from the skin cells of patients with TSC. These "induced" stem cells can be gene-edited to repair the disease-causing mutation in TSC1 or 2, and can be turned into neurons as well. This technology may ultimately enable a personalized medicine approach to TSC, wherein disease mechanisms can be identified and therapeutics tested directly in a patient's own cells.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
