Functional roles and therapeutic targeting of gelatinase B and chemokines in multiple sclerosis

Lancet Neurol. 2003 Dec;2(12):747-56. doi: 10.1016/s1474-4422(03)00587-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Chemokines / physiology*
  • Drug Delivery Systems / methods*
  • Humans
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / physiology*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / enzymology
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / metabolism*

Substances

  • Chemokines
  • Matrix Metalloproteinase 9