Fainardi E et al. (2006) Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler 12: 294–301

Matrix metalloproteinase 9 (MMP9) levels in serum and cerebrospinal fluid (CSF) are known to be elevated in patients with multiple sclerosis; these patients also have lower than normal levels of tissue inhibitor of metalloproteinase 1 (TIMP1), an inhibitor of MMP9. The MMP9:TIMP1 ratio has been proposed as a biomarker of multiple sclerosis activity. Fainardi et al. measured MMP9 activity and TIMP1 levels in 61 consecutive patients with multiple sclerosis; patients with other neurological disorders acted as controls.

Mean CSF levels of active MMP9, CSF MMP9:TIMP1 ratios, and intrathecal MMP9 synthesis were substantially higher in patients with multiple sclerosis than in those with noninflammatory neurological disorders. The serum MMP9:TIMP1 ratio was higher in patients with multiple sclerosis and in those with other inflammatory disorders than in patients with noninflammatory disorders. Patients with clinical and MRI evidence of active disease had higher serum levels of active MMP9, higher serum MMP9:TIMP1 ratios and higher intrathecal production of active MMP9 than patients with stable disease, but CSF levels of active MMP9 and CSF active MMP9:TIMP1 ratios were elevated only in patients with gadolinium-enhancing lesions on MRI.

The results suggest that high CSF levels of active MMP9 are selectively associated with multiple sclerosis, while high serum MMP9 is also found in other inflammatory neurological disorders. CSF and serum ratios of active MMP9 to TIMP1 are an important indicator of disease activity, with high CSF levels of active MMP9 associated with more-severe disease.