A COMBINED INHIBITOR OF MATRIX METALLOPROTEINASE ACTIVITY AND TUMOR-NECROSIS-FACTOR-ALPHA PROCESSING ATTENUATES EXPERIMENTAL AUTOIMMUNE NEURITIS

Matrix metalloproteinases (MMPs) and the cytokine tumour necrosis fact or (TNF)-alpha are implicated in the pathology of inflammatory demyeli nating diseases of the CNS, and may also be involved in peripheral dem yelinating diseases such as acute inflammatory demyelinating polyradic uloneuropathy. We have tested an inhibitor of MMP activity and TNF-alp ha processing, BB-1101, in experimental autoimmune neuritis (EAN), an animal model of Guillain-Barre syndrome. Treatment with BB-1101 from t he time of immunization prevented the development of EAN, and when giv en from the onset of symptoms, it significantly reduced disease severi ty. These results indicate that MMPs and/or TNF-alpha are involved in the pathogenesis of EAN, and that drugs of this type may have potentia l as novel therapeutic agents in the therapy of peripheral nervous sys tem demyelinating diseases.