Title: CNS-targeted LIF expression improves therapeutic efficacy and limits autoimmune-mediated demyelination in a model of multiple sclerosis
Authors: Slaets, Helena
Hendriks, Jerome Ja
Van Den Haute, Chris
Coun, Frea
Baekelandt, Veerle
Stinissen, Piet
Hellings, Niels # ×
Issue Date: Apr-2010
Publisher: Academic Press
Series Title: Molecular Therapy vol:18 issue:4 pages:684-691
Abstract: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with an inflammatory and a neurodegenerative component. The neuropoietic cytokine leukemia inhibitory factor (LIF) is expressed in MS lesions, but its effect on lesion development is far from understood. LIF is an interesting candidate for MS therapy, as it has neuroprotective properties and may also promote the survival of myelinating oligodendrocytes (OLGs). However, therapeutic administration of LIF is complicated by its limited ability to cross the blood-brain barrier and its pleiotropic actions outside the CNS. In this study, lentiviral vectors (LVs) were used to achieve stable expression and secretion of LIF in the CNS of adult mice. CNS-targeted expression of LIF significantly reduced demyelination in a murine model of MS. In addition, local expression of LIF ameliorated clinical symptoms with enhanced efficacy compared to systemic treatment with recombinant protein. These findings demonstrate that gene therapeutic administration of LIF is a promising approach to limit lesion burden and clinical symptoms in neuroinflammatory disease.
ISSN: 1525-0016
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group for Neurobiology and Gene Therapy
× corresponding author
# (joint) last author

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