Remyelination-promoting human IgMs: Developing a therapeutic reagent for demyelinating disease

A. E. Warrington, M. Rodriguez

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Promoting remyelination following injury to the central nervous system (CNS) promises to be an effective neuroprotective strategy to limit the loss of surviving axons and prevent disability. Studies confirm that multiple sclerosis (MS) and spinal cord injury lesions contain myelinating cells and their progenitors. Recruiting these endogenous cells to remyelinate may be of therapeutic value. This review addresses the use of antibodies reactive to CNS antigens to promote remyelination. Antibody-induced remyelination in a virus-mediated model of chronic spinal cord injury was initially observed in response to treatment with CNS reactive antisera. Monoclonal mouse and human IgMs, which bind to the surface of oligodendrocytes and myelin, were later identified that were functionally equivalent to antisera. A recombinant form of a human remyelination-promoting IgM (rHIgM22) targets areas of CNS injury and promotes maximal remyelination within 5 weeks after a single low dose (25 μg/kg). The IgM isoform of this reparative antibody is required for in vivo function. We hypothesize that the IgM clusters membrane domains and associated signaling molecules on the surface of target cells. Current therapies for MS are designed to modulate inflammation. In contrast, remyelination promoting IgMs are the first potential therapeutic molecules designed to induce tissue repair by acting within the CNS at sites of damage on the cells responsible for myelin synthesis.

Original languageEnglish (US)
Pages (from-to)213-239
Number of pages27
JournalCurrent Topics in Microbiology and Immunology
Volume318
DOIs
StatePublished - 2008

Fingerprint

Demyelinating Diseases
Central Nervous System
Immunoglobulin M
Myelin Sheath
Spinal Cord Injuries
Multiple Sclerosis
Antibodies
Immune Sera
Nervous System Trauma
Therapeutics
Oligodendroglia
Axons
Protein Isoforms
Stem Cells
Viruses
Inflammation
Antigens
Membranes
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Immunology
  • Microbiology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

Remyelination-promoting human IgMs : Developing a therapeutic reagent for demyelinating disease. / Warrington, A. E.; Rodriguez, M.

In: Current Topics in Microbiology and Immunology, Vol. 318, 2008, p. 213-239.

Research output: Contribution to journalArticle

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