Contributions
Abstract: P1123
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Oxidative stress plays a central role in multiple sclerosis (MS) pathology leading to neurodegeneration and disease progression. Recent research indicates that apart from reactive oxygen species (ROS), reactive nitrogen species (RNS), in particular the free radical nitric oxide (NOx) may be a driving factor in MS pathology by promoting DNA damage, mitochondrial dysfunction, axonal swelling and transection and neuronal apoptosis. So far there are some reports investigating NOx in cerebrospinal fluid, but the role of serum NOx in MS remains largely unclear.
Objective: We aimed to investigate the role of serum NOx in a larger cohort of MS patients compared to healthy donors (HD) and assess its relation to clinical data.
Methods: The study included 214 samples from 29 clinically isolated syndrome (CIS) (mean age 36.4 SD 9.7 years), 109 MS (mean age 36.3 SD 9.3 years) patients and 79 HD (36.2 SD 9.0 years). Among CIS/MS patients 86 (62.3%) received disease modifying therapy (Interferon beta N=53, Glatiramer acetate N=13, Natalizumab N=20). Serum NOx concentration was determined by a spectrophotometric analysis and quantification of its metabolites nitrate and nitrite using the nitrate reductase and Griess reaction method (Nitric Oxide Quantitation Kit, Active Motif).
Results: We found increased serum NOx levels in untreated (median 9.2 IQR 7.3-14.1 µM) (p< 0.01) compared to treated MS patients (median 6.6 IQR 4.9-10.3 µM) and HD (median 7.6 IQR 5.8-10.9 µM). Serum NOx levels were comparable among different MS therapies and MS subtypes. Only in CIS/MS we found higher serum NOx in female (median 8.9 IQR 6.1-13.4 µM) compared to male (median 6.6 IQR 4.9-9.1 µM) patients (p< 0.05). Serum NOx was unrelated to age, the Expanded Disability Status Scale (EDSS) Score, disease duration and age at disease onset.
Conclusion: Abnormal high serum NOx levels are present in untreated MS patients, which are reduced to levels of HD under effective immunomodulatory therapy. Female MS patients seem to be more affected by an imbalanced NOx serum status. Future studies are needed to investigate if serum NOx may serve as a marker to monitor disease activity and treatment efficacy in MS.
Disclosure: F. Hallwirth: trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
D. Moser: nothing to disclose.
M.M. Voortman: received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
P. Greiner: nothing to disclose.
S. Fuchs: serves on scientific advisory boards and / or has received speaker honoraria from Biogen Idec, Novartis, Genzyme, Merck, TEVA Pharmaceutical Industries, Sanofi Aventis and Roche.
C. Enzinger: has received funding for travel and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Shire, Novartis Genzyme and Teva Pharmaceutical Industries Ltd./sanofi-aventis; research support from Merck Serono, Biogen Idec., and Teva Pharmaceutical Industries Ltd./sanofi-aventis; is serving on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd./sanofiaventis; and has acted as academic editor for PLOSOne.
G. Bachmaier: nothing to disclose.
H-J. Gruber: nothing to disclose.
F. Fazekas: serves on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva Pharmaceutical Industries Ltd.; serves on the editorial boards of Multiple Sclerosis, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides services for Actelion and Parexel and has received speaker honoraria and support from Almirall, Merck Serono, Novartis, Pfizer, Roche, Shire and Teva Pharmaceutical Industries Ltd.
M. Khalil: has received funding for travel and speaker honoraria from Bayer Schering Pharma, Novartis Genzyme, Merck Serono, Biogen Idec and Teva Pharmaceutical Industries Ltd. and a research grant from Teva Pharmaceutical Industries Ltd.
Abstract: P1123
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Oxidative stress plays a central role in multiple sclerosis (MS) pathology leading to neurodegeneration and disease progression. Recent research indicates that apart from reactive oxygen species (ROS), reactive nitrogen species (RNS), in particular the free radical nitric oxide (NOx) may be a driving factor in MS pathology by promoting DNA damage, mitochondrial dysfunction, axonal swelling and transection and neuronal apoptosis. So far there are some reports investigating NOx in cerebrospinal fluid, but the role of serum NOx in MS remains largely unclear.
Objective: We aimed to investigate the role of serum NOx in a larger cohort of MS patients compared to healthy donors (HD) and assess its relation to clinical data.
Methods: The study included 214 samples from 29 clinically isolated syndrome (CIS) (mean age 36.4 SD 9.7 years), 109 MS (mean age 36.3 SD 9.3 years) patients and 79 HD (36.2 SD 9.0 years). Among CIS/MS patients 86 (62.3%) received disease modifying therapy (Interferon beta N=53, Glatiramer acetate N=13, Natalizumab N=20). Serum NOx concentration was determined by a spectrophotometric analysis and quantification of its metabolites nitrate and nitrite using the nitrate reductase and Griess reaction method (Nitric Oxide Quantitation Kit, Active Motif).
Results: We found increased serum NOx levels in untreated (median 9.2 IQR 7.3-14.1 µM) (p< 0.01) compared to treated MS patients (median 6.6 IQR 4.9-10.3 µM) and HD (median 7.6 IQR 5.8-10.9 µM). Serum NOx levels were comparable among different MS therapies and MS subtypes. Only in CIS/MS we found higher serum NOx in female (median 8.9 IQR 6.1-13.4 µM) compared to male (median 6.6 IQR 4.9-9.1 µM) patients (p< 0.05). Serum NOx was unrelated to age, the Expanded Disability Status Scale (EDSS) Score, disease duration and age at disease onset.
Conclusion: Abnormal high serum NOx levels are present in untreated MS patients, which are reduced to levels of HD under effective immunomodulatory therapy. Female MS patients seem to be more affected by an imbalanced NOx serum status. Future studies are needed to investigate if serum NOx may serve as a marker to monitor disease activity and treatment efficacy in MS.
Disclosure: F. Hallwirth: trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
D. Moser: nothing to disclose.
M.M. Voortman: received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
P. Greiner: nothing to disclose.
S. Fuchs: serves on scientific advisory boards and / or has received speaker honoraria from Biogen Idec, Novartis, Genzyme, Merck, TEVA Pharmaceutical Industries, Sanofi Aventis and Roche.
C. Enzinger: has received funding for travel and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Shire, Novartis Genzyme and Teva Pharmaceutical Industries Ltd./sanofi-aventis; research support from Merck Serono, Biogen Idec., and Teva Pharmaceutical Industries Ltd./sanofi-aventis; is serving on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd./sanofiaventis; and has acted as academic editor for PLOSOne.
G. Bachmaier: nothing to disclose.
H-J. Gruber: nothing to disclose.
F. Fazekas: serves on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva Pharmaceutical Industries Ltd.; serves on the editorial boards of Multiple Sclerosis, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides services for Actelion and Parexel and has received speaker honoraria and support from Almirall, Merck Serono, Novartis, Pfizer, Roche, Shire and Teva Pharmaceutical Industries Ltd.
M. Khalil: has received funding for travel and speaker honoraria from Bayer Schering Pharma, Novartis Genzyme, Merck Serono, Biogen Idec and Teva Pharmaceutical Industries Ltd. and a research grant from Teva Pharmaceutical Industries Ltd.