title: Therapeutics to promote CNS repair: a natural human neuron-binding IgM regulates membrane-raft dynamics and improves motility in a mouse model of multiple sclerosis.
abstract: We have discovered a role for natural autoantibodies in central nervous system repair, remyelination and axon protection. These natural human antibodies are of the immunoglobulin M (IgM) isotype, and they bind to the surface of neural cells. The epitope of the antibody includes sialic acid because treatment with sialidase disrupts the binding. A fully human recombinant form of one of these IgMs, rHIgM12, has the same properties as the serum-derived IgM. rHIgM12 enhanced polarized axonal outgrowth from primary neurons when presented as a substrate in vitro and improved motor functions in chronically Theiler's virus-infected SJL mice, a model of MS. rHIgM12 bound to neuronal surfaces and induced cholesterol and ganglioside (GM1) clustering, indicating that rHIgM12 functions through a mechanism of axonal membrane stabilization. Our work demonstrates that a natural human neuron-binding IgM can regulate membrane domain dynamics. This antibody has the potential to improve neurologic disease.
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Denic
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Warrington
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Bieber
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007075:Immunoglobulin M; D011994:Recombinant Proteins