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The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

L.M. Metz

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

T.R. Todoruk

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

Y. Zhang

Department of and Diagnostic Imaging, University of Calgary, Calgary, Alberta, Canada

J.R. Mitchell

Department of and Diagnostic Imaging, University of Calgary, Calgary, Alberta, Canada

M. Yeung

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

D.G. Patry

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

R.B. Bell

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

V.W. Yong

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, vyong{at}ucalgary.ca

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS. Multiple Sclerosis 2007; 13: 517-526. http://msj.sagepub.com

Key Words: adhesion molecule • interleukin-12 • MMP • multiple sclerosis • neuroimmunology • therapy

This version was published on May 1, 2007

Multiple Sclerosis, Vol. 13, No. 4, 517-526 (2007)
DOI: 10.1177/1352458506070319


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