Neuroscience 2001 Abstract
| Presentation Number: | 102.5 |
|---|---|
| Abstract Title: | THE AMPA RECEPTOR ANTAGONIST ER-167288-01 AMELIORATES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE). |
| Authors: |
Smith, T.*1
; Groom, A. J.1
; Ito, K.2
; Rivers, L.1
; Yamanishi, Y.1
1Eisai London Research Laboratories, London WC1E 6BT, United Kingdom 2Eisai Tsukuba Research Laboratories, Tsukuba, Ibaraki, Japan |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Demyelinating Disorders |
| Session: |
102. Demyelinating disorders I Poster |
| Presentation Time: | Sunday, November 11, 2001 8:00 AM-9:00 AM |
| Location: | Exhibit Hall YY-32 |
| Keywords: | Glutamate, Neuroprotection, Multiple Sclerosis, Inflammation |
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Currently, no adequate therapy is available for MS, despite immunomodulatory measures. The pathological and clinical features of MS can be reproduced in rodent models, collectively termed experimental autoimmune encephalomyelitis (EAE). Previously, we and others [Nat. Med. (2000) 6:62-66; 6:67-70] demonstrated that AMPA receptor antagonists were effective in ameliorating EAE [see also Hanada et al and Ohgoh et al SFN 2001 abstracts]. These effects were independent of immunomodulatory action suggesting either a neuro- and/or oligodendroglial-protective mechanism of action. Here we describe the effect of a potent, water soluble AMPA receptor antagonist, ER-167288-01, on the course of EAE.
Two acute EAE models in Lewis rats were used: (1) active induction with myelin basic protein (MBP) in FCA with M. tuberculosis; (2) adoptive transfer of MBP-sensitised spleen cells. ER-167288-01 (30 or 50 mg/kg; i.p. twice daily for 7 days, starting just prior to the onset of disease) dose dependently improved neurological status in the active EAE model, also reducing weight loss associated with disease but without effect on CNS inflammation. Furthermore, a significant reduction in disease severity was achieved using oral dosing with ER-167288-01 (150 mg/kg). In the adoptive transfer EAE model, 60% of vehicle animals exhibited mild symptoms of paralysis whereas 100% of the ER-167288-01-treated animals were disease free.
These results imply that therapeutic strategies for MS should be complemented by neuroprotective measures.
Two acute EAE models in Lewis rats were used: (1) active induction with myelin basic protein (MBP) in FCA with M. tuberculosis; (2) adoptive transfer of MBP-sensitised spleen cells. ER-167288-01 (30 or 50 mg/kg; i.p. twice daily for 7 days, starting just prior to the onset of disease) dose dependently improved neurological status in the active EAE model, also reducing weight loss associated with disease but without effect on CNS inflammation. Furthermore, a significant reduction in disease severity was achieved using oral dosing with ER-167288-01 (150 mg/kg). In the adoptive transfer EAE model, 60% of vehicle animals exhibited mild symptoms of paralysis whereas 100% of the ER-167288-01-treated animals were disease free.
These results imply that therapeutic strategies for MS should be complemented by neuroprotective measures.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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