title: A combined inhibitor of matrix metalloproteinase activity and tumour necrosis factor-alpha processing attenuates experimental autoimmune neuritis.
abstract: Matrix metalloproteinases (MMPs) and the cytokine tumour necrosis factor (TNF)-alpha are implicated in the pathology of inflammatory demyelinating diseases of the CNS, and may also be involved in peripheral demyelinating diseases such as acute inflammatory demyelinating polyradiculoneuropathy. We have tested an inhibitor of MMP activity and TNF-alpha processing, BB-1101, in experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré 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-alpha 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.
authors.affiliation: Department of Neurology, Medical School, London, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Redford
authors.forename: K J
authors.initials: KJ
authors.lastname: Smith
authors.forename: N A
authors.initials: NA
authors.lastname: Gregson
authors.forename: M
authors.initials: M
authors.lastname: Davies
authors.forename: P
authors.initials: P
authors.lastname: Hughes
authors.forename: A J
authors.initials: AJ
authors.lastname: Gearing
authors.forename: K
authors.initials: K
authors.lastname: Miller
authors.forename: R A
authors.initials: RA
authors.lastname: Hughes
mesh_terms: D000818:Animals; D001593:Benzyl Compounds; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000201:enzymology*; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009444:Neuritis, Autoimmune, Experimental / Q000503:physiopathology* / Q000517:prevention & control; D010431:Pentoxifylline / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000201:enzymology; D013386:Succinates; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: C101468:BB 1101; D001593:Benzyl Compounds; D004338:Drug Combinations; D011480:Protease Inhibitors; D013386:Succinates; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D018093:Gelatinases; D008666:Metalloendopeptidases; D010431:Pentoxifylline