Taking ageing into account in remyelination-based therapies for multiple sclerosis

MS is a disease that patients can suffer from over several decades. The effects of ageing are therefore likely to have a bearing on the natural history of the disease and the manner in which it is treated. In this review we consider how age affects remyelination, a spontaneously occurring regenerative process that follows demyelination and that often fails in MS patients. Over the last ten years several studies based on experimental rodent models of demyelination/remyelination have led to a clearer understanding of the age-associated changes in the environmental signals that govern remyelination, and reveal broad concepts shared by stem/precursor cell mediated regenerative processes in other tissues. Less clear is how age affects the intrinsic properties and responsiveness of the adult stem/precursor cells responsible for remyelination. We argue that the effects of age and in particular age-associated cell-intrinsic changes may be fundamental to the clinical success of pro-remyelination therapies, the development of which is currently the focus of intensive research activity.