SUPPRESSION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN THE LEWIS RAT BY THE MATRIX METALLOPROTEINASE INHIBITOR RO31-9790

Matrix metalloproteinases (MMPs) are implicated in the tissue destruct ion associated with inflammatory demyelinating diseases such as multip le sclerosis. The effect of a hydroxamate inhibitor of MMPs, Ro31-9790 , on inflammatory demyelination was assessed in two acute models of ex perimental allergic encephalomyelitis (EAE). Daily intraperitoneal inj ections of Ro31-9790 (50mgkg(-1)), beginning either at the time of dis ease induction or from day 3 post induction, significantly reduced the clinical severity of adoptively transferred EAE. Administration of th e inhibitor from the day of induction of active EAE prevented disease onset in 9/10 animals. However, in a repeat study, in which clinical d isease was much more severe in the vehicle treated animals, the inhibi tor was less effective. Clinical signs and CNS histopathology correlat ed well, with greater numbers of inflammatory lesions associated with increased disease severity. The present study confirms a role for the MMP cascade in inflammation in EAE.