Direct gene transfer to the CNS prevents emergence of neurologic disease in a murine model of mucopolysaccharidosis type I

► Intracerebroventricular infusion of AAV8 vector into neonatal MPA I mice. ► Long-term, widespread α-L-iduronidase expression in the brain. ► IDUA expression in neurons of the limbic system and Purkinje cells of the cerebellum. ► AAV treatment results in normalization of storage materials in all brain regions. ► Treatment prevented neurocognitive deficit in a Morris water maze test.