Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis.

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Brundula V, Rewcastle NB, Metz LM, Bernard CC, Yong VW

Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis.

Brain. 2002 Jun;125(Pt 6):1297-308.

PubMed ID

12023318 [ View in PubMed

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Abstract

Multiple sclerosis is characterized by the infiltration of leukocytes into the CNS. As matrix metalloproteinases (MMPs) facilitate the passage of leukocytes across matrix barriers, we tested the hypothesis that targeting MMPs could attenuate neuro-inflammation. We report that minocycline, a widely used generic drug with a good safety record, inhibited MMP activity, reduced production of MMP-9 and decreased the transmigration of T lymphocytes across a fibronectin matrix barrier. In addition, minocycline was efficacious against both mild and severe experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis. When severe EAE was produced, minocycline pre-treatment delayed the course of the disease: when maximal disease activity occurred in vehicle-treated EAE mice, minocycline animals were relatively normal and had minimal signs of inflammation and demyelination in the CNS. When tested in mice afflicted with mild EAE, minocycline attenuated the clinical severity of disease throughout the course of treatment. These results indicate that minocycline may constitute a safe and inexpensive therapy for multiple sclerosis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Minocycline	Matrix metalloproteinase-9	Protein	Humans	Unknown	Inhibitor	Details