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

F. Ruffini, R. Furlan, P. L. Poliani, E. Brambilla, P. C. Marconi, A. Bergami, G. Desina, J. C. Glorioso, G. Comi, G. Martino

Research output: Contribution to journalArticle

Abstract

The development of therapies aimed to promote remyelination is a major issue in chronic inflammatory demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis (MS), where the permanent neurological impairment is due to the axonal loss resulting from recurrent episodes of immune-mediated demyelination. Here, we show that the intrathecal injection of a herpes simplex virus (HSV) type-1 replication-defective multigene vector, engineered with the human fibroblast growth factor (FGF)-II gene (TH:bFGF vector), was able to significantly revert in C57BL/6 mice the clinicopathological signs of chronic experimental autoimmune encephalomyelitis (EAE), the animal model of MS. The treatment with the TH:bFGF vector was initiated within 1 week after the clinical onset of EAE and was effective throughout the whole follow-up period (ie 60 days). The disease-ameliorating effect 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 space (ependymal, choroidal and leptomeningeal cells); (2) significant decrease (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) significant increase (P <0.01) of the number of oligodendrocyte precursors and of myelin-forming oligodendrocytes in areas of demyelination and axonal loss. Our results indicate that CNS gene therapy using HSV-1-derived vector coding for neurotrophic factors (ie FGF-II) is a safe and non-toxic approach that might represent a potential useful 'alternative' tool for the future treatment of immune-mediated demyelinating diseases.

Original languageEnglish
Pages (from-to)1207-1213
Number of pages7
JournalGene Therapy
Volume8
Issue number16
DOIs
Publication statusPublished - 2001

Keywords

  • Experimental autoimmune encephalomyelitis
  • Fibroblast growth factor-II
  • HSV-1 vectors
  • Multiple sclerosis
  • Oligodendrocyte precursors

ASJC Scopus subject areas

  • Genetics

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