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

Gene Therapy volume 8, pages 1207–1213 (2001)Cite this article

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.

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Acknowledgements

This work was in part supported by Telethon (Italy), Italian Multiple Sclerosis Society (AISM), IRCCS (Progetti Finalizzati) and Armenise-Harvard Foundation.

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Authors and Affiliations

  1. Department of Neuroscience, Neuroimmunology Unit, DIBIT-San Raffaele Scientific Institute, Milano, Italy

    F Ruffini, R Furlan, PL Poliani, E Brambilla, A Bergami & G Martino

  2. Department of Microbiology, University of Ferrara, Ferrara, Italy

    PC Marconi

  3. Department of Neurology, Casa Sollievo della Sofferenza Scientific Institute, San Giovanni Rotondo (FG), Italy

    G Desina

  4. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    JC Glorioso

  5. Department of Neurology, San Raffaele Scientific Institute, Milano, Italy

    G Comi & G Martino

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  1. F Ruffini
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  2. R Furlan
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  9. G Comi
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  10. G Martino
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Ruffini, F., Furlan, R., Poliani, P. et al. Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice. Gene Ther 8, 1207–1213 (2001). https://doi.org/10.1038/sj.gt.3301523

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