title: Remyelination induced by a DNA aptamer in a mouse model of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a debilitating inflammatory disease of the central nervous system (CNS) characterized by local destruction of the insulating myelin surrounding neuronal axons. With more than 200 million MS patients worldwide, the absence of treatments that prevent progression or induce repair poses a major challenge. Anti-inflammatory therapies have met with limited success only in preventing relapses. Previous screening of human serum samples revealed natural IgM antibodies that bind oligodendrocytes and promote both cell signaling and remyelination of CNS lesions in an MS model involving chronic infection of susceptible mice by Theiler's encephalomyelitis virus and in the lysolecithin model of focal demyelination. This intriguing result raises the possibility that molecules with binding specificity for oligodendrocytes or myelin components may promote therapeutic remyelination in MS. Because of the size and complexity of IgM antibodies, it is of interest to identify smaller myelin-specific molecules with the ability to promote remyelination in vivo. Here we show that a 40-nucleotide single-stranded DNA aptamer selected for affinity to murine myelin shows this property. This aptamer binds multiple myelin components in vitro. Peritoneal injection of this aptamer results in distribution to CNS tissues and promotes remyelination of CNS lesions in mice infected by Theiler's virus. Interestingly, the selected DNA aptamer contains guanosine-rich sequences predicted to induce folding involving guanosine quartet structures. Relative to monoclonal antibodies, DNA aptamers are small, stable, and non-immunogenic, suggesting new possibilities for MS treatment.
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors: Branislav
authors: B
authors: Nastasijevic
authors: Brent R
authors: BR
authors: Wright
authors: John
authors: J
authors: Smestad
authors: Arthur E
authors: AE
authors: Warrington
authors: Moses
authors: M
authors: Rodriguez
authors: L James
authors: LJ
authors: Maher
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000494:pharmacology / Q000627:therapeutic use*; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017945:Theilovirus / Q000276:immunology
chemical_list: D052157:Aptamers, Nucleotide