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

R. K. Zabad, L. M. Metz, T. R. Todoruk, Y. Zhang, Joseph Ross Mitchell, M. Yeung, D. G. Patry, R. B. Bell, V. Wee Yong

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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 metal loprotei nase-9 was decreased by treatment. Thus, clinical and MRI outcomes are suRqorted by systemic immunological changes and call for further investigation of minocycline in MS.

Original languageEnglish (US)
Pages (from-to)517-526
Number of pages10
JournalMultiple Sclerosis
Volume13
Issue number4
DOIs
StatePublished - May 2007
Externally publishedYes

Fingerprint

Minocycline
Multiple Sclerosis
Gadolinium
Magnetic Resonance Imaging
Interleukin-12 Receptors
Interleukin-12 Subunit p40
Recurrence
Relapsing-Remitting Multiple Sclerosis
Vascular Cell Adhesion Molecule-1
Therapeutics
Immune Sera
Animal Models
Metals

Keywords

  • Adhesion molecule
  • Interleukin-12
  • MMP
  • Multiple sclerosis
  • Neuroimmunology
  • Therapy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Zabad, R. K., Metz, L. M., Todoruk, T. R., Zhang, Y., Mitchell, J. R., Yeung, M., ... Yong, V. W. (2007). The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: A pilot study. Multiple Sclerosis, 13(4), 517-526. https://doi.org/10.1177/1352458506070319

The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes : A pilot study. / Zabad, R. K.; Metz, L. M.; Todoruk, T. R.; Zhang, Y.; Mitchell, Joseph Ross; Yeung, M.; Patry, D. G.; Bell, R. B.; Yong, V. Wee.

In: Multiple Sclerosis, Vol. 13, No. 4, 05.2007, p. 517-526.

Research output: Contribution to journalArticle

Zabad, RK, Metz, LM, Todoruk, TR, Zhang, Y, Mitchell, JR, Yeung, M, Patry, DG, Bell, RB & Yong, VW 2007, 'The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: A pilot study', Multiple Sclerosis, vol. 13, no. 4, pp. 517-526. https://doi.org/10.1177/1352458506070319
Zabad, R. K. ; Metz, L. M. ; Todoruk, T. R. ; Zhang, Y. ; Mitchell, Joseph Ross ; Yeung, M. ; Patry, D. G. ; Bell, R. B. ; Yong, V. Wee. / The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes : A pilot study. In: Multiple Sclerosis. 2007 ; Vol. 13, No. 4. pp. 517-526.
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