Remyelination induced by a DNA aptamer in a mouse model of multiple sclerosis. PLoS One 2012;7(6):e39595
Date
07/05/2012Pubmed ID
22761835Pubmed Central ID
PMC3384608DOI
10.1371/journal.pone.0039595Scopus ID
2-s2.0-84862984026 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
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.
Author List
Nastasijevic B, Wright BR, Smestad J, Warrington AE, Rodriguez M, Maher LJ 3rdAuthor
John Smestad PhD, BS, MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAptamers, Nucleotide
Axons
Demyelinating Diseases
Disease Models, Animal
Female
Mice
Multiple Sclerosis
Myelin Sheath
Nerve Fibers, Myelinated
Spinal Cord
Theilovirus
