The Matrix Metalloproteinases Panel in Multiple Sclerosis Patients Treated with Natalizumab: A Possible Answer to Natalizumab Non- Responders

Title:The Matrix Metalloproteinases Panel in Multiple Sclerosis Patients Treated with Natalizumab: A Possible Answer to Natalizumab Non- Responders

Volume: 17 Issue: 6

Author(s): Rodica Balasa, Ciurba Bianca, Voidezan Septimiu, Simu Iunius, Hutanu Adina, Andone Sebastian*, Romaniuc Andreea, Motataianu Anca and Maier Smaranda

Affiliation:

• First Department of Neurology, County Emergency Clinical Hospital, University of Medicine and Pharmacy Targu Mures,Romania

Keywords: Multiple Sclerosis, biomarker, MMP9, Natalizumab treatment, neurodegenerative disease, central nervous system.

Abstract: 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 BBB disruption.

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.

Cite this article as:

Balasa Rodica, Bianca Ciurba, Septimiu Voidezan, Iunius Simu, Adina Hutanu, Sebastian Andone*, Andreea Romaniuc, Anca Motataianu and Smaranda Maier, The Matrix Metalloproteinases Panel in Multiple Sclerosis Patients Treated with Natalizumab: A Possible Answer to Natalizumab Non- Responders, CNS & Neurological Disorders - Drug Targets 2018; 17 (6) . https://dx.doi.org/10.2174/1871527317666180703102536