Human IgM antibodies, and diagnostic and therapeutic uses thereof particularly in the central nervous system
申请人:Mayo Foundation
公开号:US20030185827A1
公开(公告)日:2003-10-02
Antibodies, and particularly human antibodies, are disclosed that demonstrate activity in the treatment of demyelinating diseases as well as other diseases of the central nervous system that are of viral, bacterial or idiopathic origin, including neural dysfunction caused by spinal cord injury. Neuromodulatory agents are set forth that include and comprise a material selected from the group consisting of an antibody capable of binding structures or cells in the central nervous system, a peptide analog, a hapten, active fragments thereof, agonists thereof, mimics thereof, monomers thereof and combinations thereof. The neuromodulatory agent has one or more of the following characteristics: it is capable of inducing remyelination; binding to neural tissue; promoting Ca
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signaling with oligodendrocytes; and promoting cellular proliferation of glial cells. Amino acid and DNA sequences of exemplary antibodies are disclosed. Methods are described for treating demyelinating diseases, and diseases of the central nervous system of humans and domestic animals, using polyclonal IgM antibodies and human monoclonal antibodies sHIgm22(LYM 22), sHIgm46(LYM46) ebvHIgM MSI19D10, CB2bG8, AKJR4, CB2iE12, CB2iE7, MSI19E5 and MSI10E10, active fragments thereof and the like. The invention also extends to the use of human antibodies, fragments, peptide derivatives and like materials, and their use in diagnostic and therapeutic applications, including screening assays for the discovery of additional antibodies that bind to cells of the nervous system, particularly oligodendrocytes.
抗体,特别是人类抗体,被披露具有在治疗脱髓鞘性疾病以及其他中枢神经系统疾病方面的活性,这些疾病可能是病毒、细菌或特发性起因的,包括脊髓损伤引起的神经功能障碍。提出了包括并由选自抗体、肽类类似物、半抗原、其活性片段、激动剂、模拟物、单体以及它们的组合的材料的神经调节剂。神经调节剂具有以下一个或多个特征:能够诱导再髓鞘化;结合神经组织;促进寡脑细胞与Ca2+信号传导;促进胶质细胞的细胞增殖。披露了示例抗体的氨基酸和DNA序列。描述了使用多克隆IgM抗体和人类单克隆抗体sHIgm22(LYM 22)、sHIgm46(LYM46)、ebvHIgM MSI19D10、CB2bG8、AKJR4、CB2iE12、CB2iE7、MSI19E5和MSI10E10及其活性片段等等来治疗人类和家畜的脱髓鞘性疾病和中枢神经系统疾病的方法。该发明还涉及使用人类抗体、片段、肽类衍生物和类似材料,以及它们在诊断和治疗应用中的使用,包括用于筛选发现与神经系统细胞,特别是寡脑细胞结合的其他抗体的筛选分析。