title: Quantifying Beta-Galactosylceramide Kinetics in Cerebrospinal Fluid of Healthy Subjects Using Deuterium Labeling.
abstract: Therapeutics promoting myelin synthesis may enhance recovery in demyelinating diseases, such as multiple sclerosis. However, no suitable method exists to quantify myelination. The turnover of galactosylceramide (myelin component) is indicative of myelination in mice, but its turnover has not been determined in humans. Here, six healthy subjects consumed 120 mL 70% D2O daily for 70 days to label galactosylceramide. We then used mass spectrometry and compartmental modeling to quantify the turnover rate of galactosylceramide in cerebrospinal fluid. Maximum deuterium enrichment of body water ranged from 1.5-3.9%, whereas that of galactosylceramide was much lower: 0.05-0.14%. This suggests a slow turnover rate, which was confirmed by the model-estimated galactosylceramide turnover rate of 0.00168 day-1, which corresponds to a half-life of 413 days. Additional studies in patients with multiple sclerosis are needed to investigate whether galactosylceramide turnover could be used as an outcome measure in clinical trials with remyelination therapies.
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: Kms
authors.initials: K
authors.lastname: Kanhai
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Goulooze
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: J L
authors.initials: JL
authors.lastname: Hay
authors.affiliation: Experimental Medicine, Biogen Cambridge, Massachusetts, USA.
authors.forename: G
authors.initials: G
authors.lastname: Dent
authors.affiliation: Experimental Medicine, Biogen Cambridge, Massachusetts, USA.
authors.forename: A
authors.initials: A
authors.lastname: Verma
authors.affiliation: Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Hankemeier
authors.affiliation: Analytical Biochemical Laboratory BV, Assen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: de Boer
authors.affiliation: Analytical Biochemical Laboratory BV, Assen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Meijering
authors.affiliation: Experimental Medicine, Biogen Cambridge, Massachusetts, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Chavez
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: A F
authors.initials: AF
authors.lastname: Cohen
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Groeneveld
mesh_terms: D000328:Adult; D000368:Aged; D001834:Body Water; D002518:Ceramides / Q000134:cerebrospinal fluid*; D003903:Deuterium / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009005:Monosaccharides / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D002518:Ceramides; D009005:Monosaccharides; C511581:beta-galactosyl ceramide; D003903:Deuterium