A combined inhibitor of matrix metalloproteinase activity and tumour necrosis factor-α processing attenuates experimental autoimmune neuritis

Abstract

Matrix metalloproteinases (MMPs) and the cytokine tumour necrosis factor (TNF)-α are implicated in the pathology of inflammatory demyelinating diseases of the CNS, and may also be involved in peripheral demyelinating diseases such as acute inflammation demyelinating polyradiculoneuropathy. We have tested an inhibitor of MMP activity and TNF-α processing, BB-1101, in experimental autoimmune neuritis (EAN), an animal model of Guillain-Barre syndrome. Treatment with BB-1101 from the time of immunization prevented the development of EAN, and when given from the onset of symptoms, it significantly reduced disease severity. These results indicate that MMPs and/or TNF-α are involved in the pathogenesis of EAN, and that drugs of this type may have potential as novel therapeutic agents in the therapy of peripheral nervous system demyelinating diseases.