ABSTRACT
The peripheral delivery of drugs in patients affected by central nervous system (CNS)-confined diseases is therapeutically ineffective because of the presence of the blood-brain barrier (BBB), which forms an inaccessible wall to the majority of CNS targeting molecules. When ‘therapeutic’ molecules have been systemically administered to patients affected by a chronic inflammatory demyelinating disease of the CNS, such as multiple sclerosis (MS), results have been disappointing. A successful therapeutic approach in MS should therefore consider the delivery of ‘therapeutic’ molecules directly into the CNS in order to inhibit blood-borne CNS-confined mononuclear cells acting as ultimate effector cells, to rescue surviving oligodendrocytes, or to induce oligodendrocyte progenitor migration and differentiation into demyelinating areas. Biological and physical vectors engineered with heterologous genes coding for anti-inflammatory cytokines and/or growth factors might represent the appropriate tool to deliver therapeutic genes into the CNS. Here we provide a brief review of the various gene therapy attempts made so far in experimental demyelination and a critical overview of the advantages and disadvantages of the different delivery techniques employed.
