Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis.
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.
Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: lenka.novakova@vgregion.se.
Lenka
L
Novakova
Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Markus
M
Axelsson
Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Clas
C
Malmeström
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
Henrik
H
Zetterberg
Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
Ingemar
I
Björkhem
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Virginija Danylaité
VD
Karrenbauer
Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Jan
J
Lycke
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000134:cerebrospinal fluid*; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D000069442:Natalizumab / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D006888:Hydroxycholesterols; D007155:Immunologic Factors; D000069442:Natalizumab; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol
24S-hydroxycholesterol; 27-hydroxycholesterol; Biomarkers; Blood-brain barrier; Cerebrospinal fluid; Cerebrosterol; Multiple sclerosis; Natalizumab; Neurodegeneration; Neurofilament; SDMT