Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis.

Abstract:

BACKGROUND:Natalizumab therapy reduces inflammation and degeneration of the CNS in relapsing-remitting multiple sclerosis (RRMS). In cerebrospinal fluid (CSF) the concentration of 24S-hydroxycholesterol (24OHC) reflect neurodegeneration, whereas 27-hydroxycholesterol (27OHC) is dependent on the integrity of the blood-brain barrier (BBB). OBJECTIVE:To measure the impact from natalizumab treatment on 24OHC and 27OHC concentrations in serum and CSF of RRMS. METHODS:In serum and CSF obtained from 31 patients before and following 12 months of natalizumab treatment, 24OHC and 27OHC were analyzed by isotope-dilution mass spectrometry. RESULTS:Natalizumab treatment reduced CSF-24OHC concentrations (p=0.002), CSF-27OHC concentrations (p=0.01) and serum-24OHC concentrations (p=0.029). There was no significant effect of the treatment on serum-27OHC concentrations. Serum concentrations of 24OHC correlated with Symbol Digit Modalities Test scores before (r=0.5, p=0.007) and after natalizumab treatment (r=0.403, p=0.033). CONCLUSIONS:We showed for the first time that natalizumab treatment of RRMS reduced the concentrations of 24- and 27OHC in CSF, indicating reduced neurodegeneration and improved integrity of the BBB, respectively. Our results imply a role for serum 24OHC as a biomarker of cognition (visuo-spatial ability and processing speed) in RRMS.

journal_name

J Neurol Sci

authors

Novakova L,Axelsson M,Malmeström C,Zetterberg H,Björkhem I,Karrenbauer VD,Lycke J

doi

10.1016/j.jns.2015.08.1537

subject

Has Abstract

pub_date

2015-11-15 00:00:00

pages

201-6

issue

1-2

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(15)02033-X

journal_volume

358

pub_type

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