Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab

Objective: The impact of present disease‐modifying treatments (DMTs) in multiple sclerosis (MS) on nerve injury and reactive astrogliosis is still unclear. Therefore, we studied the effect of natalizumab treatment on the release of 2 brain‐specific tissue damage markers into cerebrospinal fluid (CSF) in MS patients. Methods: CSF samples from 92 patients with relapsing forms of MS were collected in a prospective manner prior to natalizumab treatment and after 6 or 12 months. In 86 cases, natalizumab was used as second‐line DMT due to breakthrough of disease activity. The levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were determined using highly sensitive in‐house developed enzyme‐linked immunosorbent assays. Results: Natalizumab treatment led to a 3‐fold reduction of NFL levels, from a mean value of 1,300 (standard deviation [SD], 2,200) to 400 (SD, 270) ng/l (p < 0.001). The later value was not significantly different from that found in healthy control subjects (350ng/l; SD, 170; n = 28). Subgroup analysis revealed a consistent effect on NFL release, regardless of previous DMT or whether patients had relapses or were in remission within 3 months prior to natalizumab treatment. No differences between pre‐ and post‐treatment levels of GFAP were detected. Interpretation: Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti‐inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability. Ann Neurol 2010