PREVENTION OF ACUTE AUTOIMMUNE ENCEPHALOMYELITIS AND ABROGATION OF RELAPSES IN MURINE MODELS OF MULTIPLE-SCLEROSIS BY THE PROTEASE INHIBITOR D-PENICILLAMINE

The in vitro activity of gelatinase B, an enzyme whose appearance in t he cerebrospinal fluid is associated with inflammatory diseases of the central nervous system, was dose-dependently inhibited by the antirhe umatic D-penicillamine. Inhibition of gelatinase B in electrophoretica lly 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 mic e, developing acute demyelination, D-penicillamine significantly reduc ed the mortality and morbidity rates of experimental allergic encephal omyelitis (EAE). In chronic relapsing EAE in Biozzi AB/H mice, an anim al model for relapses in multiple sclerosis (MS), it attenuated the ex acerbations, even when the treatment was started after the primary ful l-blown disease had developed. We infer protease inhibition as the mec hanism of action of D-penicillamine and suggest that its use may be ef fective as peroral treatment for MS.