Remyelination Trials: Are We Expecting the Unexpected?

Neuroaxonal loss is believed to underpin the progressive disability that characterizes multiple sclerosis (MS). While focal inflammatory demyelination is a principal cause of acute axonal transection and subsequent axonal degeneration, the gradual attrition of permanently demyelinated axons may also contribute to tissue damage, particularly in the progressive phase of the disease. Therefore, remyelination is considered a putative neuroprotective strategy. In this article, we review the potential pitfalls of remyelination trials, provide a framework for their appropriate design and temper the expectations, at times unrealistic, of researchers, regulators and the pharmaceutical industry.