Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice

The development of therapies aimed to promote remyelination is a major issu e in chronic inflammatory demyelinating disorders of the central nervous sy stem (CNS) such as multiple sclerosis (MS), where the permanent neurologica l impairment is due to the axonal loss resulting from recurrent episodes of immune-mediated demyelination. Here, we show that the intrathecal injectio n of a herpes simplex virus (HSV) type-1 replication-defective multigene ve ctor, engineered with the human fibroblast growth factor (FGF)-II gene (TH. -bFGF vector), was able to significantly revert in C57BL/6 mice the clinico pathological signs of chronic experimental autoimmune encephalomyelitis (EA E), the animal model of MS. The treatment with the TH:bFGF vector was initi ated within 1 week after the clinical onset of EAE and was effective throug hout the whole follow-up period (ie 60 days). The disease-ameliorating effe ct in FGF-II-treated mice was associated with: (1) CNS production of FGF-II from vector-infected cells which were exclusively located around the CSF s pace (ependymal, choroidal and leptomeningeal cells); (2) significant decre ase (P < 0.01) of the number of myelinotoxic cells (T cells and macrophages ) both in the CNS parenchyma and in the leptomeningeal space; and (3) signi ficant increase (P < 0.01) of the number of oligodendrocyte precursors and of myelin-forming oligodendrocytes in areas of demyelination and axonal los s. Our results indicate that CNS gene therapy using HSV-1-derived vector co ding for neurotrophic factors (ie FGF-II) is a safe and non-toxic approach that might represent a potential useful 'alternative' tool for the future t reatment of immune-mediated demyelinating diseases.