Human IgM antibodies, and diagnostic and therapeutic uses thereof particularly in the central nervous system

摘要

Antibodies, particularly human antibodies, are disclosed having activity in treatment of demyelinating diseases and diseases of the central nervous system. Neuromodulatory agents are provided comprising a material selected from the group consisting of an antibody capable of binding structures or cells in the central nervous system, a peptide analog, and active fragments, monomers and combinations thereof having one or more of the following characteristics: capable of inducing remyelination; binding to neural tissue; promoting Ca++ 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, using polyclonal IgM antibodies and human monoclonal antibodies sHIgm22(LYM 22), sHIgm46(LYM46) ebvHIgM MSI19D10, CB2bG8, AKJR4, CB2iE12, CB2iE7, MSI19E5 and MSI10E10, and active fragments thereof. The invention extends to the use of antibodies and fragments in diagnostic and therapeutic applications, including screening assays.

主权项

1. A method of stimulating remyelination of central nervous system axons in a mammal, which method comprises:
exogenously administering to said mammal an effective amount of a pharmaceutical composition comprising a recombinant antibody capable of binding oligodendrocytes and capable of inducing remyelination, having a heavy chain sequence comprising the heavy chain variable region CDR1, CDR2 and CDR3 sequences as set out in FIG. 71 and SEQ ID NO:49 and a light chain sequence comprising the light chain variable region CDR1, CDR2 and CDR3 sequences as set out in FIG. 72 and SEQ ID NO:51, or a monomer or an active fragment thereof wherein the monomer or active fragment comprises the heavy chain variable region CDR1, CDR2 and CDR3 sequences as set out in FIG. 71 and SEQ ID NO:49 and the light chain variable region CDR1, CDR2 and CDR3 sequences as set out in FIG. 72 and SEQ ID NO:51, and a pharmaceutically acceptable carrier, vehicle, or diluent.