The ependymal route to the CNS: an emerging gene-therapy approach for MS

The systemic administration of anti-inflammatory molecules to patients affected by immune-mediated inflammatory demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis, has limited therapeutic efficacy owing to the presence of the blood-brain barrier. The delivery of drugs to the CNS using a nonreplicative viral vector engineered with genes encoding anti-inflammatory cytokines might represent an alternative therapeutic strategy. Here, we propose accessing the CNS through the ependymal-leptomeningeal route. This approach is based on the injection of nonreplicative vectors into the cerebrospinal fluid space. These vectors are able to infect the ependymal and leptomeningeal cells consistently and without side effects, and in turn, produce the 'therapeutic' product of the transgene in the CNS for extended periods of time. This strategy could represent an alternative treatment for inflammatory neurological disorders when systemic immunosuppressive therapies fail to control the evolution of disease satisfactorily.