A recombinant human IgM promotes myelin repair after a single, very low dose.
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.
Warrington
Arthur E
AE
Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. warrington.authur@mayo.edu
Bieber
Allan J
AJ
Ciric
Bogoljub
B
Pease
Larry R
LR
Van Keulen
Virginia
V
Rodriguez
Moses
M
D000818:Animals; D000918:Antibody Specificity; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000494:pharmacology*; D008657:Metabolic Clearance Rate; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects* / Q000276:immunology; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D016896:Treatment Outcome
D007075:Immunoglobulin M; D011993:Recombinant Fusion Proteins