Treatment of ischemic episodes and cerebroprotection through Prostaglandin E2 (PGE2) EP2 and/or EP4 receptor agonists
The present invention provides compositions and methods for treating an ischemic episode using PGE 2 EP 2 agonists and/or PGE 2 EP 4 agonists alone or in combination with anti-thrombotic agents.
1 . A method of treating an ischemic episode in a subject, the method comprising administering to said subject a therapeutically effective amount of a therapeutic agent selected from the group consisting of PGE 2 EP 2 agonists, PGE 2 EP 4 agonists, mixed PGE 2 EP 2 /EP 4 agonists, and mixtures or metabolic precursors thereof.
2 . The method of claim 1 , wherein the ischemic episode is caused by stroke or cardiac arrest.
3 . The method of claim 1 , wherein the therapeutic agent is misoprostol or an analog of misoprostol.
4 . The method of claim 1 , wherein the therapeutic agent is ONO-AE1-329 or an analog of ONO-AE1-329.
5 . A method of treating or preventing a neurological disorder resulting from exposure of neurons to ischemia in a subject, the method comprising administering to said subject a therapeutically effective amount of a therapeutic agent selected from the group consisting of PGE 2 EP 2 agonists, PGE 2 EP 4 agonists, mixed PGE 2 EP 2 /EP 4 agonists, and mixtures or metabolic precursors thereof.
6 . The method of claim 5 , wherein said ischemia is caused by stroke or cardiac arrest.
7 . The method of claim 5 , wherein the therapeutic agent is misoprostol or an analog of misoprostol.
8 . The method of claim 5 , wherein the therapeutic agent is ONO-AE1-329 or an analog of ONO-AE1-329.
9 . A method of screening a candidate compound for efficacy in treating an ischemic episode, the method comprising
(a) assaying said compound for activation of the PGE 2 EP 2 and/or PGE 2 EP 4 receptor to determine an PGE 2 EP 2 agonist, PGE 2 EP 4 agonist or mixed PGE 2 EP 2 /EP 4 agonist;
(b) contacting a model for said ischemic episode with said PGE 2 EP 2 agonist, PGE 2 EP 4 agonist or mixed PGE 2 EP 2 /EP 4 agonist; and
(c) determining the efficacy of said PGE 2 EP 2 agonist, PGE 2 EP 4 agonist or mixed PGE 2 EP 2 /EP 4 agonist in treating said ischemic episode.
10 . A pharmaceutical composition comprising (a) a therapeutic agent selected from the group consisting of PGE 2 EP 2 agonists, PGE 2 EP 4 agonists, mixed PGE 2 EP 2 /EP 4 agonists, and mixtures, metabolic precursors or pharmaceutically acceptable derivatives thereof; and (b) an anti-thrombotic agent or a pharmaceutically acceptable derivative thereof; in a mixture with a pharmaceutically acceptable carrier.
11 . The pharmaceutical composition according to claim 10 , wherein (a) the therapeutic agent is misoprostol or an analog of misoprostol and (b) the anti-thrombotic agent is tissue plasminogen activator.
12 . The pharmaceutical composition according to claim 10 , wherein (a) the therapeutic agent is ONO-AE1-329 or an analog of ONO-AE1-329 and (b) the anti-thrombotic agent is tissue plasminogen activator.
13 . A method of treating an ischemic episode in a subject, the method comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition according to claim 10 , 11 or 12 .
14 . A method of treating or preventing a neurological disorder resulting from exposure of neurons to ischemia in a subject, the method comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition according to claim 10 , 11 or 12 .