Background: In the lymphocyte migration across the blood-brain barrier (BBB) in multiple
sclerosis (MS), matrix metalloproteinases (MMPs) play an important role in the degradation of the basal
membrane. Natalizumab (NAT), a monoclonal antibody, binds to the alpha-4 (α4) integrin leading
to BBB impermeability. Approximately 30% of NAT-treated patients show clinical or MRI signs of
Objective: To determine whether NAT significantly influences the MMPs serum levels and to what
extent these could be used as biomarkers in relapsing-remitting MS (RRMS) patients.
Materials and Methods: This prospective study over a period of 8 months of NAT treatment, included
30 RRMS patients (mean age 38 ± 6 years; mean MS duration 12 ± 5 years), of which ten were initially
naive to NAT and 15 were healthy controls. We determined the serum levels of the MMPs Panel
(MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13) quantified by a
multiplex method at the beginning and end of the study.
Results: After 8 months of NAT treatment, a statistically significant decrease was found in MMP9,
MMP2, MMP3, MMP8, and MMP10 levels. Relapses during the study were correlated with a variation
of MMP12 and MMP13 serum levels. MMP9 had the most numerous correlations with the EDSS
score, Rio score, and duration of NAT treatment. MMPs signature (the sum of all MMPs) and the
MMP9/MMP2 ratio significantly decreased during the study.
Conclusion: 1. The serum level of MMP9 significantly decreased by NAT treatment and correlates
with MS activity; 2. After eight months of NAT treatment, the MMPs signature and the MMP9/MMP2
ratio decreased; 3. MMP9 might be used as a biomarker in MS patients treated with NAT.