J Neurol. 2003 Sep;250(9):1037-43
Dubois MD PhD B, Leary MRCP SM, Nelissen I, Opdenakker MD PhD G, Giovannoni PhD G, Thompson MD AJ.
Institute of Neurology, London, UK.
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.
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.
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.
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.
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.