Effects of Natalizumab Treatment on the Cerebrospinal Fluid Proteome of Multiple Sclerosis Patients

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.