Therapeutic strategies in multiple sclerosis. II. Long-term repair

Spontaneous myelin repair in multiple sclerosis (MS) provides a. striking e xample of the brain's inherent capacity for sustained and stable regenerati ve tissue repair-but also clearly emphasizes the limitations of this capaci ty; remyelination ultimately fails widely in many patients, and disability and handicap accumulate. The observation of endogenous partial myelin repai r has raised the possibility that therapeutic interventions designed to sup plement or promote remyelination might have a useful and significant impact both in the short term, in restoring conduction, and in the long term, in safeguarding axons. Therapeutic remyelination interventions must involve ma nipulations to either the molecular or the cellular environment within lesi ons; both depend crucially on a detailed understanding of the biology of th e repair process and of those glia implicated in spontaneous repair, or cap able of contributing to exogenous repair. Here we explore the biology of myelin repair in MS, examining the glia resp onsible for successful remyelination, oligodendrocytes and Schwann cells, t heir 'target' cells, neurons and the roles of astrocytes. Options for thera peutic remyelinating strategies are reviewed, including glial cell transpla ntation and treatment with growth factors or other soluble molecules. Clini cal aspects of remyelination therapies are considered-which patients, which lesions, which stage of the disease, and how to monitor an intervention-an d the remaining obstacles and hazards to these approaches are discussed.