title: Serum Gelatinases Levels in Multiple Sclerosis Patients during 21 Months of Natalizumab Therapy.
abstract: Background. Natalizumab is a highly effective treatment approved for multiple sclerosis (MS). The opening of the blood-brain barrier mediated by matrix metalloproteinases (MMPs) is considered a crucial step in MS pathogenesis. Our goal was to verify the utility of serum levels of active MMP-2 and MMP-9 as biomarkers in twenty MS patients treated with Natalizumab. Methods. Serum levels of active MMP-2 and MMP-9 and of specific tissue inhibitors TIMP-1 and TIMP-2 were determined before treatment and for 21 months of therapy. Results. Serum levels of active MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 did not differ during the treatment. The ratio between MMP-9 and MMP-2 was increased at the 15th month compared with the 3rd, 6th, and 9th months, greater at the 18th month than at the 3rd and 6th months, and higher at the 21st than at the 3rd and 6th months. Discussion. Our data indicate that an imbalance between active MMP-9 and active MMP-2 can occur in MS patients after 15 months of Natalizumab therapy; however, they do not support the use of serum active MMP-2 and active MMP-9 and TIMP-1 and TIMP-2 levels as biomarkers for monitoring therapeutic response to Natalizumab.
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44124 Ferrara, Italy.
authors.forename: Massimiliano
authors.identifier: 0000-0001-6555-6075
authors.initials: M
authors.lastname: Castellazzi
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44124 Ferrara, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bellini
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44124 Ferrara, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Trentini
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milano, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Delbue
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Elia
authors.affiliation: Department of General Neurology, National Neurological Institute C. Mondino, 27100 Pavia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Gastaldi
authors.affiliation: Department of General Neurology, National Neurological Institute C. Mondino, 27100 Pavia, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Franciotta
authors.affiliation: Department of General Neurology, National Neurological Institute C. Mondino, 27100 Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44124 Ferrara, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Manfrinato
authors.affiliation: Department of Morphology, Experimental Medicine and Surgery, University of Ferrara, 44124 Ferrara, Italy.
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Volta
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44124 Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Granieri
authors.affiliation: Department of Neurosciences and Rehabilitation, S. Anna Hospital, 44124 Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fainardi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D000069442:Natalizumab / Q000627:therapeutic use*; D011379:Prognosis; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D000069442:Natalizumab; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9