Giancarlo Comi, MD, Vita-Salute San Raffaele University, Milan, Italy, discusses the treatment possibilities for progressive multiple sclerosis (MS). The mechanisms of action of ocrelizumab and siponimod are mainly anti-inflammatory and only in minor proportions neuroprotective. Therefore, the next fundamental step is to develop treatments that directly target mechanisms of neurodegeneration. There are currently Phase II and III clinical trials exploring new possibilities in the development of neuroprotective agents for progressive MS. This interview took place during the 2022 World Congress on Controversies in Neurology (CONy) meeting.