Contributions
Abstract: EP1476
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Multiple sclerosis (MS) has a variable prognosis and lacks a reliable laboratory prognostic marker. Recent evidence suggests that an altered sphingolipid metabolism and sphingomyelinase function is associated with MS pathogenesis. Under inflammatory conditions brain endothelial cells, important components of the blood brain barrier (BBB), may secrete acid sphingomyelinase (ASM).
Objective: To evaluate if the activity and levels of circulating ASM correlate with measures of disease activity and progression.
Methods: We analyzed activity and protein levels of this enzyme in serum of 36 relapsing remitting multiple sclerosis (RRMS) patients , 24 clinically isolated syndrome (CIS) patients and 6 primary progressive multiple sclerosis (PPMS) patients. The patients were part of the six-year follow-up of an early inception cohort, in which patients were included at diagnosis and subsequently followed annually. We analyzed blood samples at baseline and year 6 follow up.
To determine ASM protein levels in the serum, the human ASM ELISA Kit (CSB-E09361h, Cusabio, Huissen The Netherlands) was used following manufacturer"s instructions.
ASM activity was quantified using the ASM assay kit (Echelon Biosciences, Salt Lake City, USA) according to manufacturer"s instructions supplemented with 0,1mM ZnCl2 and the standard curve using recombinant ASM as reference.
Preliminary Results: There were no significant cross-sectional correlations between ASM activity and MRI (enhancing lesions, T2 volumes, T1 volumes) at baseline and also no significant cross-sectional correlations between ASM activity and MRI at follow up year 6 (normalized brain volume, normalized total lesion volume, normalized grey matter volume, normalized white matter volume and normalized deep grey matter volume).
In addition, there was no predictive value of baseline ASM activity levels for measures of disease activity (relapses and MRI) and progression during six years of follow-up. The use of disease modifying treatment had no significant impact on levels of ASM activity during follow-up.
Protein levels were not detectable.
Interpretation: Although somewhat limited by sample size, ASM protein level and activity doesn"t seem to be promising biomarkers for predicting disease activity and progression in MS.
Disclosure: Disclosures
C. Leurs: received a grant from the Dutch MS research Foundation.
M. A. Lopes Pinheiro: received a grant from the Dutch MS research Foundation.
L. Wierts: nothing to disclose.
A. J.C. Eijlers: received a grant from the Dutch MS research Foundation.
L. Balk: received a research grant from TEVA.
M.P. Wattjes: serves on the editorial boards of Neuroradiology, Journal of Neuroimaging, European Radiology, Frontiers of Neurology, and serves as a consultant for Novartis and Biogen.
B.M.J. Uitdehaag: has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
J. Killestein: has accepted speaker and consulting fees from Merck-Serono, Biogen Idec, Teva, Genzyme and Novartis.
H.E. de Vries: has accepted speaker fee from Merck Serono. Received a GMSI research grant from Merck Serono and is Chief Scientific Officer at Brendinn Therapeutics.
Abstract: EP1476
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Multiple sclerosis (MS) has a variable prognosis and lacks a reliable laboratory prognostic marker. Recent evidence suggests that an altered sphingolipid metabolism and sphingomyelinase function is associated with MS pathogenesis. Under inflammatory conditions brain endothelial cells, important components of the blood brain barrier (BBB), may secrete acid sphingomyelinase (ASM).
Objective: To evaluate if the activity and levels of circulating ASM correlate with measures of disease activity and progression.
Methods: We analyzed activity and protein levels of this enzyme in serum of 36 relapsing remitting multiple sclerosis (RRMS) patients , 24 clinically isolated syndrome (CIS) patients and 6 primary progressive multiple sclerosis (PPMS) patients. The patients were part of the six-year follow-up of an early inception cohort, in which patients were included at diagnosis and subsequently followed annually. We analyzed blood samples at baseline and year 6 follow up.
To determine ASM protein levels in the serum, the human ASM ELISA Kit (CSB-E09361h, Cusabio, Huissen The Netherlands) was used following manufacturer"s instructions.
ASM activity was quantified using the ASM assay kit (Echelon Biosciences, Salt Lake City, USA) according to manufacturer"s instructions supplemented with 0,1mM ZnCl2 and the standard curve using recombinant ASM as reference.
Preliminary Results: There were no significant cross-sectional correlations between ASM activity and MRI (enhancing lesions, T2 volumes, T1 volumes) at baseline and also no significant cross-sectional correlations between ASM activity and MRI at follow up year 6 (normalized brain volume, normalized total lesion volume, normalized grey matter volume, normalized white matter volume and normalized deep grey matter volume).
In addition, there was no predictive value of baseline ASM activity levels for measures of disease activity (relapses and MRI) and progression during six years of follow-up. The use of disease modifying treatment had no significant impact on levels of ASM activity during follow-up.
Protein levels were not detectable.
Interpretation: Although somewhat limited by sample size, ASM protein level and activity doesn"t seem to be promising biomarkers for predicting disease activity and progression in MS.
Disclosure: Disclosures
C. Leurs: received a grant from the Dutch MS research Foundation.
M. A. Lopes Pinheiro: received a grant from the Dutch MS research Foundation.
L. Wierts: nothing to disclose.
A. J.C. Eijlers: received a grant from the Dutch MS research Foundation.
L. Balk: received a research grant from TEVA.
M.P. Wattjes: serves on the editorial boards of Neuroradiology, Journal of Neuroimaging, European Radiology, Frontiers of Neurology, and serves as a consultant for Novartis and Biogen.
B.M.J. Uitdehaag: has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
J. Killestein: has accepted speaker and consulting fees from Merck-Serono, Biogen Idec, Teva, Genzyme and Novartis.
H.E. de Vries: has accepted speaker fee from Merck Serono. Received a GMSI research grant from Merck Serono and is Chief Scientific Officer at Brendinn Therapeutics.