Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab
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- 8 December 2010
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 69 (1), 83-89
- https://doi.org/10.1002/ana.22247
Abstract
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 2010Keywords
This publication has 29 references indexed in Scilit:
- Natalizumab Reduces Clinical and MRI Activity in Multiple Sclerosis Patients with High Disease Activity: Results from a Multicenter Study in SwitzerlandEuropean Neurology, 2010
- Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluidMultiple Sclerosis Journal, 2009
- Combination of CSF N -acetylaspartate and neurofilaments in multiple sclerosisNeurology, 2009
- Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) studyThe Lancet Neurology, 2009
- Natalizumab is effective as second line therapy in the treatment of relapsing remitting multiple sclerosisEuropean Journal of Neurology, 2009
- Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosisMultiple Sclerosis Journal, 2008
- Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosisNeurology, 2007
- MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MSNeurology, 2007
- Axonal Transection in the Lesions of Multiple SclerosisThe New England Journal of Medicine, 1998
- Rating neurologic impairment in multiple sclerosisNeurology, 1983