Wright Brent R, Warrington Arthur E, Edberg Dale D, Rodriguez Moses
Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Arch Neurol. 2009 Dec;66(12):1456-9. doi: 10.1001/archneurol.2009.262.
Natural autoreactive monoclonal IgM antibodies have demonstrated potential as therapeutic agents for central nervous system (CNS) disease. These antibodies bind surface antigens on specific CNS cells, activating intracellular repair-promoting signals. IgM antibodies that bind to surface antigens on oligodendrocytes enhanced remyelination in animal models of multiple sclerosis. IgM antibodies that bind to neurons stimulate neurite outgrowth and prevent neuron apoptosis. The neuron-binding IgM antibodies may have utility in CNS axon- or neuron-damaging diseases, such as amyotrophic lateral sclerosis, stroke, spinal cord injury, or secondary progressive multiple sclerosis. Recombinant remyelination-promoting IgM antibodies have been generated for formal toxicology studies and, after Food and Drug Administration approval, a phase 1 clinical trial. Natural autoreactive monoclonal antibodies directed against CNS cells represent novel therapeutic molecules to induce repair of the nervous system.
天然自身反应性单克隆IgM抗体已显示出作为中枢神经系统（CNS）疾病治疗剂的潜力。这些抗体结合特定中枢神经系统细胞上的表面抗原，激活细胞内促进修复的信号。与少突胶质细胞表面抗原结合的IgM抗体可增强多发性硬化症动物模型中的髓鞘再生。与神经元结合的IgM抗体刺激神经突生长并防止神经元凋亡。与神经元结合的IgM抗体可能对中枢神经系统轴突或神经元损伤性疾病有用，如肌萎缩侧索硬化症、中风、脊髓损伤或继发进展型多发性硬化症。已经制备了重组促髓鞘再生IgM抗体用于正式的毒理学研究，并在获得美国食品药品监督管理局批准后进行了1期临床试验。针对中枢神经系统细胞的天然自身反应性单克隆抗体代表了诱导神经系统修复的新型治疗分子。
