Marchionni M A, Cannella B, Hoban C, Gao Y L, Garcia-Arenas R, Lawson D, Happel E, Noel F, Tofilon P, Gwynne D, Raine C S
Cambridge NeuroScience Inc., Massachusetts 02139, USA.
Adv Exp Med Biol. 1999;468:283-95.
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). This study has focused on recombinant human GGF2 (rhGGF2) and it's potential to affect 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 (MS). Mice with EAE were treated with rhGGF2 during both the acute and relapsing phases, and GGF2 treatment led to delayed signs, decreased severity and resulted in statistically significant reductions in relapse rate. Further, rhGGF2-treated groups displayed CNS lesions with more remyelination than in controls. This correlated with increased expression of myelin basic protein exon 2, a marker for remyelination, and with an increase of the regulatory cytokine, IL-10. Thus, a beneficial effect of a neurotrophic growth factor has been demonstrated upon the clinical, pathologic and molecular manifestations of autoimmune demyelination, an effect that was associated with increased expression of a Th2 cytokine. rhGGF2 treatment may represent a novel approach to the treatment of MS (Cannella et al., 1998).
神经胶质生长因子2(GGF2)是一种神经元信号,可促进少突胶质细胞(中枢神经系统(CNS)的髓鞘形成细胞)的增殖和存活。本研究聚焦于重组人GGF2(rhGGF2)及其对小鼠慢性复发性实验性自身免疫性脑脊髓炎(EAE)(人类脱髓鞘疾病多发性硬化症(MS)的主要动物模型)中受损髓鞘的临床恢复和修复的影响潜力。在急性期和复发期均用rhGGF2治疗患有EAE的小鼠,GGF2治疗导致症状延迟出现、严重程度降低,并使复发率在统计学上显著降低。此外,与对照组相比,rhGGF2治疗组的中枢神经系统病变有更多的髓鞘再生。这与髓鞘碱性蛋白外显子2(一种髓鞘再生标志物)的表达增加以及调节性细胞因子IL-10的增加相关。因此,已证明一种神经营养生长因子对自身免疫性脱髓鞘的临床、病理和分子表现具有有益作用,这种作用与Th2细胞因子的表达增加有关。rhGGF2治疗可能代表一种治疗MS的新方法(坎内拉等人,1998年)。