More MS news articles for Oct 2001

Matrix metalloproteinases and their tissue inhibitors as markers of disease subtype and response to interferon-b therapy in relapsing and secondary-progressive multiple sclerosis patients

Published Online: 7 Aug 2001
Annals of Neurology
Volume 50, Issue 4, 2001. Pages: 443-451

Yanina Galboiz, MSc 1, Sarah Shapiro, PhD 2, Nitza Lahat, PhD 2 4, Hannah Rawashdeh, MD 1, Ariel Miller, MD, PhD 1 3 4 *
1Neuroimmunlogy, Carmel Medical Center, Haifa
2Immunology Research Units, Carmel Medical Center, Haifa
3Rappaport Institute for Research in the Medical Sciences, Haifa
4Faculty of Medicine, Technion-Israel Institute of Technology; Haifa, Israel


Matrix metalloproteinases (MMPs) have recently been implicated in the pathogenesis of multiple sclerosis.

Their suggested role includes the disruption of the blood-brain barrier, immune cell transmigration into the central nervous system, and myelin degradation.

The present study characterized the mRNA level of a wide spectrum of MMPs and tissue inhibitors of metalloproteinases (TIMPs) expressed by peripheral blood leukocytes from relapsing-remitting (n = 16) and secondary-progressive (n = 12) multiple sclerosis patients.

The expression of the same MMPs and TIMPs was evaluated also in a prospective 12-month follow-up of 6 patients randomly chosen from each of the 2 groups during interferon-b-1a treatment.

Reverse transcription-polymerase chain reaction assessment demonstrated elevated levels of MT1-MMP and MMP-7 mRNA levels in both groups of patients, and no significant differences in MMP-9 levels, compared with healthy controls.

Divergent expression of MMP-2 between relapsing-remitting and secondary-progressive patients compared with controls was observed.

IFN-b treatment was associated with significant suppression of MMP-9 and MMP-7 mRNA in relapsing-remitting patients, though no significant changes were observed in the secondary-progressive group.

These results contribute to the understanding of the interferon-b-mediated immunomodulatory and therapeutic effects in multiple sclerosis patients and also support evidence for distinct immune mechanism(s) underlying relapsing-remitting- versus secondary-progressive multiple sclerosis.

The study also suggests that MMPs may be considered as potential biomarkers for response to treatment as well as targets for immunotherapy in multiple sclerosis.

Received: 4 May 2001; Revised: 13 June 2001; Accepted: 13 June 2001

email: Ariel Miller (

*Correspondence to Ariel Miller, Neuroimmunology Unit, Department of Neurology, Lady Davis, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel

Funded by:
 Serono Pharmaceuticals Ltd., Geneva, Switzerland
 Rappaport Family Institute for Research in the Medical Sciences
 Technion-Israel Institute of Technology, Haifa
 Israeli Ministry of Health, Jerusalem, Israel

Copyright © 2001 Wiley-Liss, Inc