title: Endogeneous remyelination: findings in human studies.
abstract: In multiple sclerosis, conduction block in demyelinated axons underlies early neurological symptoms, whereas axonal transection is believed to be responsible for more permanent later deficits. Approved treatments for the disease are immunoregulatory and reduce the rate of lesion formation and clinical exacerbation, but are only partially effective in preventing the onset of disability. Remyelination is a term for the re-generation of the nerve's myelin sheath and is a subject of active medical research. Remyelination capacity varies from patient to patient or even from lesion to lesion in one and the same patient. Efforts to understand the causes for remyelination failure have prompted research into the biology of remyelination and the complex molecular factors that regulate remyelination. In the current review article we address challenges of remyelination research with a special focus on histo-pathological studies using brain biopsy and autopsy material. We summarize our current knowledge about extent of remyelination in multiple sclerosis patients and its relation to disease duration, lesion type, inflammation, affected brain region and gender. Furthermore we will address which step(s) of the oligodendrocyte maturation program is impaired and, thus, could be a feasible target for therapeutic interventions. Specifically mentioned will be the distribution of oligodendrocyte progenitor cells in demyelinated multiple sclerosis plaques and therapeutic approaches which aim to boost intrinsic properties of progenitor cells or to supply progenitors by cell transplantation approaches. This comprehensive overview is complemented by recent findings suggesting that U.S. Food and Drug Administration-approved treatment options, such as FTY720 (Gilenya®) or glatiramer acetate (Copaxone®) might boost myelin repair.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, D-52074 Aachen, Germany. mkipp@ukaachen.de
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.forename: Marion
authors.initials: M
authors.lastname: Victor
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D058990:Molecular Targeted Therapy; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D009836:Oligodendroglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D012075:Remission, Spontaneous; D012737:Sex Factors
chemical_list: D007166:Immunosuppressive Agents