TSC1 Gene Therapy AAVerts Neurological Associated Mortality

The SVZ contains neural stem cells and transits amplifying cells, microglia, ependyma, neuroblasts, and astrocytes. [...]identifying the cells that are proliferating and determining whether this is a cell autonomous effect is important. Alternatively, enlarged neurons or astrocytes could potentially lead to megalencephaly and hydrocephalus. [...]determining the exact cause of death will be important to provide mechanistic insight into how AAV9-TSC1 rescue is exerted. Mutations that result in dominant negative function could alter tuberin or Rheb, and it is unclear whether AAV-delivered hamartin could compensate. [...]successful clinical trials would need to carefully choose patient cohorts with TSC1 mutations.