Serum gelatinase B/MMP-9 in primaryprogressive multiple sclerosis patients treated withinterferon-beta-1a

Background: Interferon- beta (IFN) acts by a variety of mechanisms inrelapsing-remitting multiple sclerosis (MS). One of these is acellular down-regulation of gelatinase B or matrixmetalloproteinase-9 (MMP-9), which is known from biochemical,biological and immunohistochemical evidences to play adisease-promoting role in MS.Aims: a) To investigate the influence of IFN-1a (30 or 60 µg I.M./week) on serum MMP-9 levels in patients with primaryprogressive MS (PPMS). b) To correlate serum MMP-9 levels withclinical and magnetic resonance imaging (MRI) findings.Methods: Serial blood samples were collected every 3 months from 49patients participating in a phase II trial of IFN-1a in PPMS.Serum MMP-9 was quantified by ELISA and correlations withclinical (EDSS) as well as MRI findings (brain and spinal cordatrophy, ventricular volume, T1 and T2 lesion load) werecalculated.Results: No significant differences were found between serial serumMMP-9 levels in IFN-treated versus placebo-treated patients. MMP-9levels did not differ between patients who progressed or did notprogress during the study interval. Although mean absolute serumMMP-9 levels over the study period correlated with an increasein T2 lesion load (relative T2 change: r=0.51, p<0.001;absolute T2 change: r=0.30, p=0.038), absolute increase in brainventricular volume (r=0.29, p=0.05) and increased brain atrophy(r=0.35, p=0.02), only the correlation with T2 lesion load wassustained throughout the study period. No correlations werefound between MMP-9 levels and relative changes in ventricularvolume or with relative/absolute changes in T1 lesion load andin spinal cord atrophy. None of the MRI measures correlated withMMP-9 changes between baseline levels and those ontreatment.Conclusion: Although some evidence suggests a down-regulating effectof IFN on MMP-9, this was not confirmed for a once weeklyintramuscular dose of IFN-1a in patients with PPMS. Thesustained correlation between serum MMP-9 and changes in T2volumes, and the lack of correlation with clinical or MRImeasures of disease progression may suggest that MMP-9 is moredirectly related to non-specific central nervous system damagethan to axonal loss.