THE NEUREGULIN, GLIAL GROWTH-FACTOR-2, DIMINISHES AUTOIMMUNE DEMYELINATION AND ENHANCES REMYELINATION IN A CHRONIC RELAPSING MODEL FOR MULTIPLE-SCLEROSIS

Glial growth factor 2 (GGF2) is a neuronal signal that promotes the pr oliferation and survival of the oligodendrocyte, the myelinating cell of the central nervous system (CNS). The present study examined whethe r recombinant human GGF2 (rhGGF2) could effect clinical recovery and r epair to damaged myelin in chronic relapsing experimental autoimmune e ncephalomyelitis (EAE) in the mouse, a major animal model for the huma n demyelinating disease, multiple sclerosis. Mice with EAE were treate d with rhGGF2 during both the acute and relapsing phases. Clinically, GGF2 treatment delayed signs, decreased severity, and resulted in stat istically significant reductions in relapse rate. rhGGF2-treated group s displayed CNS lesions with more remyelination than in controls. This correlated with increased mRNA expression of myelin basic protein exo n 2, a marker for remyelination, and with an increase in the CNS of th e regulatory cytokine, interleukin 10, at both the RNA and protein lev els. Thus, a beneficial effect of a neurotrophic growth factor has bee n demonstrated on the clinical, pathologic, and molecular manifestatio ns of autoimmune demyelination, an effect that was associated with inc reased expression of a T helper 2 cytokine. rhGGF2 treatment may repre sent a novel approach to the treatment of multiple sclerosis.