The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis

Barbara Cannella, Carolyn J. Hoban, Yan Ling Gao, Renee Garcia-Arenas, Deborah Lawson, Mark Marchionni, David Gwynne, Cedric S. Raine

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Glial growth factor 2 (GGF2) is a neuronal signal that promotes the proliferation and survival of the oligodendrocyte, the myelinating cell of the central nervous system (CNS). The present study examined whether recombinant human GGF2 (rhGGF2) could effect clinical recovery and repair to damaged myelin in chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the mouse, a major animal model for the human demyelinating disease, multiple sclerosis. Mice with EAE were treated with rhGGF2 during both the acute and relapsing phases. Clinically, GGF2 treatment delayed signs, decreased severity, and resulted in statistically significant reductions in relapse rate. rhGGF2-treated groups displayed CNS lesions with more remyelination than in controls. This correlated with increased mRNA expression of myelin basic protein exon 2, a marker for remyelination, and with an increase in the CNS of the regulatory cytokine, interleukin 10, at both the RNA and protein levels. Thus, a beneficial effect of a neurotrophic growth factor has been demonstrated on the clinical, pathologic, and molecular manifestations of autoimmune demyelination, an effect that was associated with increased expression of a T helper 2 cytokine. rhGGF2 treatment may represent a novel approach to the treatment of multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)10100-10105
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number17
DOIs
StatePublished - Aug 18 1998

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Neuregulins
Neuregulin-1
Demyelinating Diseases
Multiple Sclerosis
Autoimmune Experimental Encephalomyelitis
Central Nervous System
Cytokines
Myelin Basic Protein
Oligodendroglia
Nerve Growth Factors
Myelin Sheath
Interleukin-10
Exons
Intercellular Signaling Peptides and Proteins
Animal Models
RNA
Recurrence
Messenger RNA
Fibromatosis, Gingival, 2
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

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The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis. / Cannella, Barbara; Hoban, Carolyn J.; Gao, Yan Ling; Garcia-Arenas, Renee; Lawson, Deborah; Marchionni, Mark; Gwynne, David; Raine, Cedric S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 17, 18.08.1998, p. 10100-10105.

Research output: Contribution to journalArticle

Cannella, Barbara ; Hoban, Carolyn J. ; Gao, Yan Ling ; Garcia-Arenas, Renee ; Lawson, Deborah ; Marchionni, Mark ; Gwynne, David ; Raine, Cedric S. / The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 17. pp. 10100-10105.
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