Natalizumab is a very effective, relatively new drug for the treatment of relapsing remitting multiple sclerosis. Inflammatory and neurodegenerative processes in the central nervous system are presumed to cause adverse effects during the course of this disease. To monitor the effects of natalizumab treatment on the cerebrospinal fluid (CSF) proteome of patients, CSF samples were taken from patients before commencing treatment as well as after 1 year of treatment. Profiling proteomics experiments using electrospray Orbitrap mass spectrometry and pair wise comparison of patients before and after 1 year of natalizumab treatment revealed a number of candidate biomarkers that were significantly differentially abundant between the before and after treatment groups. Three proteins were subsequently validated using selected reaction monitoring (SRM) in a new, independent sample set. All three proteins, Ig mu chain C region and haptoglobin, both known inflammation-related proteins, as well as Chitinase-3-like protein 1, were confirmed by SRM to be significantly lower abundant in CSF of multiple sclerosis patients after 1 year of natalizumab treatment. The findings for Chitinase-3-like protein 1, a presumed biomarker for more rapid progression from a first clinically isolated syndrome to clinically definite multiple sclerosis, was further confirmed by ELISA measurements.

adult, article, cerebrospinal fluid, cerebrospinal fluid cytology, clinical article, controlled study, diagnostic test accuracy study, drug efficacy, drug monitoring, drug safety, electrospray mass spectrometry, electrospray orbitrap mass spectrometry, female, human, male, multiple sclerosis, nucleotide sequence, priority journal, protein expression, protein function, proteomics, reactor monitoring, selected reaction monitoring, sensitivity and specificity, treatment duration, treatment response
dx.doi.org/10.1021/pr3012107, hdl.handle.net/1765/40830
Journal of Proteome Research
Erasmus MC: University Medical Center Rotterdam

Stoop, M.P, Singh, V, Stingl, C, Martin, R.R, Khademi, M, Olsson, T, … Luider, T.M. (2013). Effects of natalizumab treatment on the cerebrospinal fluid proteome of multiple sclerosis patients. Journal of Proteome Research, 12(3), 1101–1107. doi:10.1021/pr3012107