Establishing the Molecular Basis of the Neurodevelopmental Features of TSC
Abstract
Tuberous sclerosis complex (TSC) is a genetic disease that causes benign tumors in several different organs, including the brain, and can begin in early childhood. TSC is caused by mutations in the genes TSC1 and TSC2. Some of the most debilitating symptoms for patients with TSC are those that are associated with the brain, such as frequent seizures, epilepsy, autism, and intellectual disability. There is currently no cure for TSC, and the symptoms associated with the brain are some of the hardest aspects of the disease to treat. If we can better understand the changes that occur in the brain of TSC patients, we can develop new targeted treatments. We have recently discovered new gene, called Unkempt, which works together with the TSC1/2 genes to control how nerve cells develop in the brain. In this project, we aim to understand how Unkempt controls nerve cell development and how this goes wrong in TSC. We will analyze the chemical changes that occur in Unkempt in human cellular models of TSC. We believe that Unkempt activity is blocked in TSC patients and so we will study a novel mouse model we have generated, which lacks the Unkempt gene in developing nerve cells in the brain, as a new animal model of TSC. We will also use established mouse models of TSC to test whether compensating for the lack of Unkempt activity can prevent the neurological problems in these mice. Within 3 years, this project will dramatically increase our understanding of the molecular and cellular changes that occur in the brain in TSC. It will also provide the basis for the development of new targeted treatments for the neurological problems associated with TSC within 5-10 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710082
Entities
People
- Joseph M. Bateman
Organizations
- United States Army