Gene therapy in autoimmune, demyelinating disease of the central nervous system

Gene Ther. 2003 May;10(10):844-53. doi: 10.1038/


Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS), where suspected autoimmune attack causes nerve demyelination and progressive neurodegeneration and should benefit from both anti-inflammatory and neuroprotective strategies. Although neuroprotection strategies are relatively unexplored in MS, systemic delivery of anti-inflammatory agents to people with MS has so far been relatively disappointing. This is most probably because of the limited capacity of these molecules to enter the target tissue, because of exclusion by the blood-brain barrier. The complex natural history of MS also means that any therapeutic agents will have to be administered long-term. Gene therapy offers the possibility of site-directed, long-term expression, and is currently being preclinically investigated in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. While some immune effects may be targeted in the periphery using DNA vaccination, strategies both viral and nonviral are being developed to target agents into the CNS either via direct delivery or using the trafficking properties of cell-carrier systems. Targeting of leucocyte activation, cytokines and nerve growth factors have shown some promising benefit in animal EAE systems, the challenge will be their application in clinical use.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Central Nervous System / pathology
  • Cytokines / genetics
  • Cytokines / immunology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / therapy
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Humans
  • Mice
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / therapy*
  • Th1 Cells / immunology
  • Vaccines, DNA / administration & dosage


  • Cytokines
  • Vaccines, DNA