Two steps forward for myelin repair in multiple sclerosis

Multiple sclerosis is a convolution of inflammation, degeneration, and variable repair, the timing and extent of which determines whether the clinical course is slow with periods of recovery or a progressive worsening of symptoms. Accordingly, to improve outcomes for patients with multiple sclerosis—particularly progressive multiple sclerosis—multipronged, combination therapies are probably needed. Existing therapies that modulate the immune system, such as alemtuzumab, are increasingly effective. 1 Giovannoni G Cohen JA Coles AJ et al. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology. 2016; 87: 1985-1992 Crossref PubMed Scopus (43) Google Scholar However, remyelination therapies designed to improve CNS repair and, in turn, protect vital axons from permanent degeneration are still in their infancy, for several reasons. First, remyelination is difficult to measure clinically, and MRI approaches have insufficient specificity to distinguish early myelin damage from remyelination, for example. Second, in contrast to robust and predictable remyelination in rodent models, 2 Jeffery ND Blakemore WF Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin. J Neurocytol. 1995; 24: 775-781 Crossref PubMed Scopus (131) Google Scholar myelin regeneration in people with multiple sclerosis is highly variable, 3 Patrikios P Stadelmann C Kutzelnigg A et al. Remyelination is extensive in a subset of multiple sclerosis patients. Brain. 2006; 129: 3165-3172 Crossref PubMed Scopus (568) Google Scholar confounding the translation of promising interventions to the clinic. Lastly, remyelination capacity in all people decreases with age, 4 Goldschmidt T Antel J König FB Bruck W Kuhlmann T Remyelination capacity of the MS brain decreases with disease chronicity. Neurology. 2009; 72: 1914-1921 Crossref PubMed Scopus (268) Google Scholar yet the underlying pathophysiology remains incompletely understood. Two reports 5 Fard MK van der Meer F Sánchez P et al. BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions. Sci Transl Med. 2017; 9 (eaam7816.) Crossref PubMed Scopus (77) Google Scholar , 6 Cantuti-Castelvetri L Fitzner D Bosch-Queralt M et al. Defective cholesterol clearance limits remyelination in the aged central nervous system. Science. 2018; 359: 684-688 Crossref PubMed Scopus (228) Google Scholar have shed important new light on biomarkers for and mechanisms of myelin repair.