CNSI, rhGGF2......PNAS abstract
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, and Cedric S. Raine*,,§
Departments of * Pathology, Neurology, and § Neuroscience,
Albert Einstein College of Medicine, 1300 Morris Park Avenue,
Bronx, NY 10461; and Cambridge NeuroScience, Inc., One Kendall
Square, Building 700, Cambridge, MA 02139
Communicated by Dominick P. Purpura, Albert Einstein College
of Medicine, Bronx, NY, June 16, 1998 (received for review
April 16, 1998)
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.
eom |
