HUMAN MONOCOLONAL ANTIBODIES FOR CNS REMYELINATION

DESCRIPTION (provided by applicant): The primary goal of the current research will be to select the best recombinant form of one of two naturally occurring human igM antibodies demonstrated to stimulate remyelination to further develop for clinical testing in inflammatory demyelinating disease, such as MS. These antibodies, designated sHIgM22 and sHIgM46, were isolated by the Rodriquez laboratory at the Mayo Clinic by screening a bank of sera from patients with monoclonal gammopathy. The isolation, cloning and characterization of these antibodies were part of the specific aims of a Phase I STTR grant. The antibodies have been demonstrated to react with oligodendrocytes and to stimulate remyelination in the Theiler's Murine Encephalomyelitis Virus model in the SJL/J mouse. The specific aims of the current grant will be: Extend the characterization of each of these antibodies to the identification of the biologically relevant antigen and further elucidate the underlying mechanism by which the antibodies stimulate remyelination. Develop a robust scaleable manufacturing system that is suitable for producing commercial and clinical supplies of antibody. Extend the testing of the antibodies into other model systems of inflammatory CNS demyelinating disease and assess the toxicologic, pharmacokinetic and ADME properties of the antibodies.