A recombinant human IgM promotes myelin repair after a single, very low dose

Arthur E. Warrington, Allan J. Bieber, Bogoljub Ciric, Larry R. Pease, Virginia Van Keulen, Moses Rodriguez

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

A recombinant human monoclonal IgM, rHIgM22, promotes the synthesis of new myelin when used to treat several animal models of demyelination. rHIgM22 binds to myelin and the surface of oligodendrocytes and accumulates at central nervous system lesions in vivo. The minimal dose of monoclonal IgM required to promote remyelination has a direct bearing on the proposed mechanism of action. A dose ranging study using rHIgM22 was performed in mice with chronic virus-induced demyelination, a model of chronic progressive multiple sclerosis. The lowest tested dose of rHIgM22 effective at promoting spinal cord remyelination was a single 500-ng intraperitoneal bolus injection. A time course study of spinal cord repair performed in chronically demyelinated mice revealed that remyelination plateaued by 5 weeks following treatment with rHIgM22. Two doses of rHIgM22 spaced 5 weeks apart did not increase the extent of remyelination over a single dose. The half-life of rHIgM22 in the mouse systemic circulation was determined to be 15 hr; the human IgM serum concentration was close to zero by 48 hr following antibody administration. We propose that the specificity of rHIgM22 for myelin on living tissue targets the antibody to demyelinated lesions, initiating a long-term reparative effect on the central nervous system.

Original languageEnglish (US)
Pages (from-to)967-976
Number of pages10
JournalJournal of Neuroscience Research
Volume85
Issue number5
DOIs
StatePublished - Apr 2007

Keywords

  • Multiple sclerosis
  • Oligodendrocyte
  • Spinal cord repair
  • Theiler's murine encephalomyelitis virus

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Warrington, A. E., Bieber, A. J., Ciric, B., Pease, L. R., Van Keulen, V., & Rodriguez, M. (2007). A recombinant human IgM promotes myelin repair after a single, very low dose. Journal of Neuroscience Research, 85(5), 967-976. https://doi.org/10.1002/jnr.21217