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Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a.
J Neurol. 2003 Sep; 250(9):1037-43.JN

Abstract

BACKGROUND

Interferon- beta (IFNbeta) acts by a variety of mechanisms in relapsing-remitting multiple sclerosis (MS). One of these is a cellular down-regulation of gelatinase B or matrix metalloproteinase-9 (MMP-9), which is known from biochemical, biological and immunohistochemical evidences to play a disease-promoting role in MS.

AIMS

a) To investigate the influence of IFNbeta-1a (30 or 60 micro g I. M./week) on serum MMP-9 levels in patients with primary progressive MS (PPMS). b) To correlate serum MMP-9 levels with clinical and magnetic resonance imaging (MRI) findings.

METHODS

Serial blood samples were collected every 3 months from 49 patients participating in a phase II trial of IFNbeta-1a in PPMS. Serum MMP-9 was quantified by ELISA and correlations with clinical (EDSS) as well as MRI findings (brain and spinal cord atrophy, ventricular volume, T1 and T2 lesion load) were calculated.

RESULTS

No significant differences were found between serial serum MMP-9 levels in IFNbeta-treated versus placebo-treated patients. MMP-9 levels did not differ between patients who progressed or did not progress during the study interval. Although mean absolute serum MMP-9 levels over the study period correlated with an increase in T2 lesion load (relative T2 change: r=0.51, p<0.001; absolute T2 change: r=0.30, p=0.038), absolute increase in brain ventricular volume (r=0.29, p=0.05) and increased brain atrophy (r=0.35, p=0.02), only the correlation with T2 lesion load was sustained throughout the study period. No correlations were found between MMP-9 levels and relative changes in ventricular volume or with relative/absolute changes in T1 lesion load and in spinal cord atrophy. None of the MRI measures correlated with MMP-9 changes between baseline levels and those on treatment.

CONCLUSION

Although some evidence suggests a down-regulating effect of IFNbeta on MMP-9, this was not confirmed for a once weekly intramuscular dose of IFNbeta-1a in patients with PPMS. The sustained correlation between serum MMP-9 and changes in T2 volumes, and the lack of correlation with clinical or MRI measures of disease progression may suggest that MMP-9 is more directly related to non-specific central nervous system damage than to axonal loss.

Authors+Show Affiliations

Institute of Neurology, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14504963

Citation

Dubois, Bénédicte, et al. "Serum Gelatinase B/MMP-9 in Primary Progressive Multiple Sclerosis Patients Treated With Interferon-beta-1a." Journal of Neurology, vol. 250, no. 9, 2003, pp. 1037-43.
Dubois B, Leary SM, Nelissen I, et al. Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a. J Neurol. 2003;250(9):1037-43.
Dubois, B., Leary, S. M., Nelissen, I., Opdenakker, G., Giovannoni, G., & Thompson, A. J. (2003). Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a. Journal of Neurology, 250(9), 1037-43.
Dubois B, et al. Serum Gelatinase B/MMP-9 in Primary Progressive Multiple Sclerosis Patients Treated With Interferon-beta-1a. J Neurol. 2003;250(9):1037-43. PubMed PMID: 14504963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a. AU - Dubois,Bénédicte, AU - Leary,Siobhan M, AU - Nelissen,Inge, AU - Opdenakker,Ghislain, AU - Giovannoni,Gavin, AU - Thompson,Alan J, PY - 2002/03/01/received PY - 2003/02/17/revised PY - 2003/02/28/accepted PY - 2003/9/25/pubmed PY - 2003/12/10/medline PY - 2003/9/25/entrez SP - 1037 EP - 43 JF - Journal of neurology JO - J Neurol VL - 250 IS - 9 N2 - BACKGROUND: Interferon- beta (IFNbeta) acts by a variety of mechanisms in relapsing-remitting multiple sclerosis (MS). One of these is a cellular down-regulation of gelatinase B or matrix metalloproteinase-9 (MMP-9), which is known from biochemical, biological and immunohistochemical evidences to play a disease-promoting role in MS. AIMS: a) To investigate the influence of IFNbeta-1a (30 or 60 micro g I. M./week) on serum MMP-9 levels in patients with primary progressive MS (PPMS). b) To correlate serum MMP-9 levels with clinical and magnetic resonance imaging (MRI) findings. METHODS: Serial blood samples were collected every 3 months from 49 patients participating in a phase II trial of IFNbeta-1a in PPMS. Serum MMP-9 was quantified by ELISA and correlations with clinical (EDSS) as well as MRI findings (brain and spinal cord atrophy, ventricular volume, T1 and T2 lesion load) were calculated. RESULTS: No significant differences were found between serial serum MMP-9 levels in IFNbeta-treated versus placebo-treated patients. MMP-9 levels did not differ between patients who progressed or did not progress during the study interval. Although mean absolute serum MMP-9 levels over the study period correlated with an increase in T2 lesion load (relative T2 change: r=0.51, p<0.001; absolute T2 change: r=0.30, p=0.038), absolute increase in brain ventricular volume (r=0.29, p=0.05) and increased brain atrophy (r=0.35, p=0.02), only the correlation with T2 lesion load was sustained throughout the study period. No correlations were found between MMP-9 levels and relative changes in ventricular volume or with relative/absolute changes in T1 lesion load and in spinal cord atrophy. None of the MRI measures correlated with MMP-9 changes between baseline levels and those on treatment. CONCLUSION: Although some evidence suggests a down-regulating effect of IFNbeta on MMP-9, this was not confirmed for a once weekly intramuscular dose of IFNbeta-1a in patients with PPMS. The sustained correlation between serum MMP-9 and changes in T2 volumes, and the lack of correlation with clinical or MRI measures of disease progression may suggest that MMP-9 is more directly related to non-specific central nervous system damage than to axonal loss. SN - 0340-5354 UR - https://www.unboundmedicine.com/medline/citation/14504963/Serum_gelatinase_B/MMP_9_in_primary_progressive_multiple_sclerosis_patients_treated_with_interferon_beta_1a_ L2 - https://dx.doi.org/10.1007/s00415-003-0110-8 DB - PRIME DP - Unbound Medicine ER -