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Gene Therapy-Mediated Modulation of Immune Processes in the Central Nervous System

[ Vol. 9 , Issue. 24 ]

Author(s):

Roberto Furlan, Stefano Pluchino and Gianvito Martino   Pages 2002 - 2008 ( 7 )

Abstract:


Selective interference with immune processes in the central nervous system (CNS) is a very difficult task because of the limitations associated with the delivery of immuno modulatory molecules across the blood brain barrier. Systemic administration of immune-mediators, either by conventional routes or by intramuscularly or intravenous gene therapy, is hampered by severe side effects and alters immune-system functions also in peripheral organs. To overcome these problems, different gene therapy strategies have been developed to deliver immuno modulatory molecules directly within the central nervous system. The use of engineered CNS antigenspecific circulating cells as selective delivery vehicles, the direct injection of gene vectors into the brain parenchyma, or also the ependymal route, have been proposed as possible alternative gene therapy protocols to selectively interfere with immuno-pathological processes in the CNS. We will review the use of these CNS-targeted gene therapy protocols for the treatment of experimental autoimmune encephalomyelitis (EAE), the prototypical experimental immune-mediated disease of the CNS, and therefore discuss the relevance of these results for the therapy of multiple sclerosis (MS) the most common, immune-mediated, demyelinating disease of the CNS in humans.

Keywords:

gene therapy, central nervous system, multiple sclerosis, experimental autoimmune encephalomyelitis, cytokines, growth factors

Affiliation:

Neuroimmunology Unit- DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan,Italy.



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