To evaluate the effects of minocycline on circulating matrix metalloproteinases (MMPs) in people with clinically isolated syndrome (CIS).

Most people with a CIS have a second inflammatory event (relapse or new MRI activity) within 6 months. The Minocycline in CIS Trial (MinoCIS; clinicaltrials.gov NCT00666887) showed that 100 mg of minocycline twice daily reduces conversion of CIS to 2005 McDonald criteria multiple sclerosis (MS)compared to placebo, over 6 months. The treatment effect was statistically significant at 3 months. Confirming early onset of action would support the use of minocycline as a bridge therapy from symptom onset until longer term therapy is started. Minocycline inhibits MMPs, crucial regulators of immune/inflammatory demyelination. Its effect on these biomarkers may provide clues to its onset of action.  

Serum was collected at each visit during the MinoCIS trial. MMP concentrations were measured using a commercially available multiplex assay at baseline and month 1 in an unselected subset of paired samples from 28 participants (mean age 37.8, 75% female).

In this pilot study MMP-1, 7 and TIMP-1 decreased from baseline to month 1; MMP-12 increased. The effects were significant only in the minocycline group. MMP-7 concentrations were higher at baseline in those who converted to MS and it correlated with the presence of baseline Gad + lesions and T2 lesion volume. 

In this pilot study MMP-7 was associated with conversion to MS and imaging markers of higher risk of activity and disability in MS. After 1 month, minocycline treatment (but not placebo) significantly reduced the concentrations of several MMPs, including MMP-7. MMP-7 his highly expressed in active demyelinating lesions and in circulating immune cells in people with MS. These effects were evident early after treatment initiation. This could partly account for its clinical benefit and supports an early effect. Confirmation will be undertaken using remaining trial samples.