Gene Therapy to Extend Lifespan of Tsc1 Conditional Brain Knockouts

Narrative that briefly one paragraph describes the subject, purpose and scope of the research. Tuberous sclerosis complex TSC is an autosomal genetic disorder which affects about 1 in 6,000 newborns. The disease is caused by inactivating mutations in either of two related tumor suppressor genes, TSC1 encoding hamartin or TSC2 encoding tuberin. The TSC proteins regulate the mTOR pathway and are critical in cell growth and proliferation. TSC gene carriers are born with one defective copy and if they lose the normal copy is somatic tissues, pathologic lesions develop which can affect multiple organs in the body. Focal pathologic lesions in the brain, including cortical tubers and subependymal nodules, are seen in the majority 90 of TSC patients, and disrupt neuronal architecture causing epilepsy and obstruction of ventricles, respectively Short et al., 1995. In a magnetic resonance imaging MRI study about one third of subependymal nodules were observed to grow over a 4-year period postnatally Katz et al., 2012 with the potential to block cerebrospinal fluid CSF flow leading to fatal hydrocephalus. Early surgical removal of subependymal nodules has been recommended, but has neurosurgical risks Berhouma, 2010.