Gene Therapy to Extend Lifespan of Tsc1 Conditional Brain Knockouts
Abstract
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).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2015
- Accession Number
- AD1001282
Entities
People
- Xandra O. Breakefield
Organizations
- Massachusetts General Hospital