Comparison of ventricular and intravenous lentiviral-mediated gene therapy for murine MPS VII

The blood-brain barrier is not completely impervious to lysosomal enzymes, therefore, therapeutic enzyme can be distributed widely throughout the brain via the extensive cerebral vasculature. However, improvements in somatic gene delivery and expression are required for this to be completely successful. Ventricular vector delivery cleared lysosomal storage within the CNS making this a reasonable, albeit more challenging, therapeutic option for the MPS. The best therapeutic outcomes, with possible synergistic effects within the CNS, might be expected to occur when vector delivery to the brain is used in combination with somatic gene transfer.