Current immunomodulatory therapies for multiple sclerosis fail to adequately address the axonal/neuronal degeneration which underlies the gradual neurological decline associated with the disease. Blockade of the glutamate AMPA receptor, which confers protection in a variety of models of neurodegeneration, ameliorates experimental autoimmune encephalomyelitis (EAE) [Nat. Med. (2000) 6:62-66; 6:67-70; see also Yamauchi et al SFN, 2002 and Smith et al SFN, 2002]. Disease amelioration was realised independently of immunosuppression, suggesting either a neuro- and/or oligodendroglial-protective mechanism of action. Here, we describe the pronounced synergistic effect of combination of interferon-β (IFN-β) with E2007, a potent, water-soluble AMPA receptor antagonist [profiled in Tokuhara et al and Hashizume et al SFN, 2002], on the course of EAE in Lewis rats. E2007 alone (5 and 10 mg/kg; p.o. 7-16 days post immunisation) dose dependently improved neurological status whereas IFN-β (1x106 IU/rat s.c.) was without ...