Cytokine gene therapy of autoimmune demyelination revisited using herpes simplex virus type-1-derived vectors

G. Martino, P. L. Poliani, P. C. Marconi, G. Comi, R. Furlan

Research output: Contribution to journalArticle

Abstract

The peripheral delivery of drugs in patients affected by central nervous system (CNS)-confined diseases is therapeutically ineffective due to the presence of the blood-brain barrier which forms an inaccessible wall to the majority of CNS targeting molecules. When molecules with an anti-inflammatory profile 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 anti-inflammatory molecules directly into the CNS in order to inhibit blood-borne CNS-confined mononuclear cells which act as ultimate effector cells directly destroying oligodendrocytes and/or releasing myelinotoxic substances. Biological and physical vectors engineered with heterologous genes coding for immunomodulatory cytokines with an anti-inflammatory profile might represent the appropriate tool to deliver therapeutic genes into the CNS of patients with MS. So far, cytokine gene therapy has never been attempted in MS, but encouraging results have been obtained in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), using viral vectors or plasmids engineered with cytokine genes and then injected systemically, either in the blood stream or circulating encephalitogenic T cells, or into the CNS. Here, we critically discuss the various attempts made in EAE using gene therapy protocols based on the delivery of immunomodulatory cytokine genes. Special emphasis is put on the use of non-replicative herpes simplex type-1 (HSV)-derived vectors engineered with the gene of the immunomodulatory cytokine interleukin (IL)-4.

Original languageEnglish
Pages (from-to)1087-1093
Number of pages7
JournalGene Therapy
Volume7
Issue number13
Publication statusPublished - Jul 2000

Keywords

  • Cytokines
  • EAE
  • Gene therapy
  • Herpetic vectors
  • Inflammation
  • MS

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Cytokine gene therapy of autoimmune demyelination revisited using herpes simplex virus type-1-derived vectors'. Together they form a unique fingerprint.

  • Cite this