Indeed, due to various activities, not least those of the International Progressive MS Alliance, there has been a remarkable surge of awareness for the unmet needs of people with progressive multiple sclerosis. Clearly, a precise understanding of the mechanisms of neurodegeneration in progressive multiple sclerosis is an essential prerequisite for achieving therapeutic progress. In this regard, glutamatergic mechanisms are certainly not the only potential target. Others include voltage-gated sodium channels (as a target for phenytoin8) and other ion channels, 4 metabolic pathways (eg, as targets for high-dose biotin9 and statins10), and remyelination. 11 With intensified research, the aim of finding a neuroprotective therapy for progressive multiple sclerosis might not be unrealistic.