Prevention of acute autoimmune encephalomyelitis and abrogation of relapses in murine models of multiple sclerosis by the protease inhibitor D-penicillamine

Inflamm Res. 1995 Dec;44(12):529-34. doi: 10.1007/BF01757357.


The in vitro activity of gelatinase B, an enzyme whose appearance in the cerebrospinal fluid is associated with inflammatory diseases of the central nervous system, was dose-dependently inhibited by the antirheumatic D-penicillamine. Inhibition of gelatinase B in electrophoretically pure preparations and in cell culture supernatants and human body fluids was obtained at dosages reached in the circulation of patients treated with a peroral dosis of 750 mg D-penicillamine per day. In mice, developing acute demyelination, D-penicillamine significantly reduced the mortality and morbidity rates of experimental allergic encephalomyelitis (EAE). In chronic relapsing EAE in Biozzi AB/H mice, an animal model for relapses in multiple sclerosis (MS), it attenuated the exacerbations, even when the treatment was started after the primary full-blown disease had developed. We infer protease inhibition as the mechanism of action of D-penicillamine and suggest that its use may be effective as peroral treatment for MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Blotting, Northern
  • Chronic Disease
  • Collagenases / cerebrospinal fluid
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Humans
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Multiple Sclerosis / prevention & control*
  • Penicillamine / therapeutic use*
  • Protease Inhibitors / therapeutic use*
  • Recurrence


  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Collagenases
  • Matrix Metalloproteinase 9
  • Penicillamine