Neuroscience 2002 Abstract
| Presentation Number: | 36.15 |
|---|---|
| Abstract Title: | SYNERGISTIC EFFECT OF THE AMPA RECEPTOR ANTAGONIST, E2007 AND INTERFERON-BETA IN AMELIORATING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE). |
| Authors: |
Smith, T.*1
; Groom, A.1
; Rivers, L.1
; Yamanishi, Y.1
1Eisai London Res. Labs. Ltd., University College London, London, United Kingdom |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Glutamate |
| Session: |
36. Neurotransmitters: glutamate--disease mechanisms Poster |
| Presentation Time: | Sunday, November 3, 2002 10:00 AM-11:00 AM |
| Location: | Hall A2-B3 C-80 |
| Keywords: | IFN-beta, Multiple Sclerosis, Neuroprotection, Axonal protection |
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 effect. In combination with IFN-β, both doses of E2007 provided increased protection compared with IFN-β or E2007 alone. This effect was most pronounced at 10 mg/kg E2007 with IFN-β, where all animals remained symptom free for the duration of treatment. These results imply that therapeutic strategies for MS should be complemented by neuroprotective measures.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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