Persistent progression despite treatment with natalizumab in patients with multiple sclerosis (MS) is said to reflect progression independent of inflammation. Therefore, this population can act as a model to investigate the non-inflammatory component of MS pathology and look for markers of axonal damage. Charlotte Teunissen, PhD, VU University Medical Center Amsterdam, The Netherlands, outlines the findings of a study assessing serum contactin-1 (sCNTN1) as a novel biomarker in natalizumab-treated relapsing-remitting MS. CNTN1 levels were shown to differ in patients that progressed on natalizumab compared to those that did not, suggesting it may be a valuable marker of long-term disease progression. Prof. Teunissen describes further work using this model to generate new biomarkers via unbiased proteomic screens. This interview took place at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress 2021.