Author:

Keywords:

Animals, Chemokines, Drug Delivery Systems, Humans, Matrix Metalloproteinase 9, Multiple Sclerosis, Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, CENTRAL-NERVOUS-SYSTEM, MATRIX-METALLOPROTEINASE EXPRESSION, MONOCYTE CHEMOTACTIC PROTEIN-3, BLOOD MONONUCLEAR-CELLS, COA REDUCTASE INHIBITOR, HUMAN MCP-3 GENE, MICROARRAY ANALYSIS, INTERFERON-BETA, CEREBROSPINAL-FLUID, 1103 Clinical Sciences, 1109 Neurosciences, Neurology & Neurosurgery, 3202 Clinical sciences, 3209 Neurosciences

Abstract:

Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of autoreactive lymphocytes, and skewing of the extracellular proteinase balance, are targets for new therapies. Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was recently shown to degrade interferon beta, one of the drugs used to treat MS. Consequently, the effect of endogenously produced interferon beta or parenterally given interferon beta may be increased by gelatinase B inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and inhibition of hydroxymethyl-glutaryl-coenzyme-A reductase to lower expression of gelatinase B, may become effective treatments of MS, alone or in combination with interferon beta. This may allow interferon beta to be used at lower doses and prevent side-effects.