Cytokine Gene Delivery into the Central Nervous System Using Intrathecally Injected Nonreplicative Viral Vectors

The delivery of drugs through the bloodstream in patients affected by central nervous system (CNS)-confined multifocal diseases can be therapeutically ineffective because of the presence of the blood-brain barrier (BBB), which forms an inaccessible wall to the majority of CNS-targeting molecules. The BBB is a specialized endothelial structure formed by the interaction between endothelial cells and astrocytes. It can be distinguished from the normal endothelium for the presence of tight junctions between endothelial cells, which are impermeable to macromolecules and even ions, and for the reduced endocytic activity, which considerably decreases the number of molecules that can cross the BBB in a nonspecific fashion (1 ). Only the presence of specific transport mechanisms assures that molecules essential for the brain metabolism (e.g., amino acids and glucose) reach the brain parenchyma.