METHODS FOR TREATING OR SCREENING FOR COMPOUNDS FOR THE TREATMENT OF SEPSIS
The present invention relates to a method for treating and screening for compounds for the treatment of sepsis. More specifically, the treatment and screening methods are based on the discovery that granzyme B containing platelets (GzmB-platelet) causes apoptosis by direct contact with cells.
1 . A method for preventing or reducing apoptosis comprising the step of contacting cells with a compound effective to prevent, reduce, or inhibit platelet aggregation.
2 . The method of claim 1 , wherein the compound is an antiplatelet drug.
3 . The method of claim 2 , wherein the antiplatelet drug is a GP2a3b antagonist, a ADP receptor/P2Y12 inhibitor, a prostaglandin analogue (PGI2), a COX inhibitor, a thromboxane inhibitor, or a phosphodiesterase inhibitor.
4 . The method of claim 3 , wherein the GP2a3b antagonist is epifibitide, tirofiban, or abciximab.
5 . The method of claim 3 , wherein the ADP receptor/P2Y12 inhibitor is clopidogrel, prasugrel, or ticlopidine.
6 . The method of claim 3 , wherein the prostaglandin analogue is beraprost, prostacyclin, iloprost, or treprostinil.
7 . The method of claim 3 , wherein the COX inhibitor is asprin, aloxiprin, carbasalate calcium, indobufen, or triflusal.
8 . The method of claim 3 , wherein the thromboxane inhibitor is dipyridamole, picotamide, or terutroban.
9 . A method for treating sepsis in a individual comprising the step of administering to an individual having a compound effective to prevent, reduce, or inhibit platelet aggregation.
10 . The method of claim 9 , wherein the compound is an antiplatelet drug.
11 . The method of claim 10 , wherein the antiplatelet drug is a GP2a3b antagonist, a ADP receptor/P2Y12 inhibitor, a prostaglandin analogue (PGI2), a COX inhibitor, a thromboxane inhibitor, or a phosphodiesterase inhibitor.
12 . The method of claim 11 , wherein the GP2a3b antagonist is epifibitide, tirofiban, or abciximab.
13 . The method of claim 11 , wherein the ADP receptor/P2Y12 inhibitor is clopidogrel, prasugrel, or ticlopidine.
14 . The method of claim 11 , wherein the prostaglandin analogue is beraprost, prostacyclin, iloprost, or treprostinil.
15 . The method of claim 11 wherein the COX inhibitor is asprin, aloxiprin, carbasalate calcium, indobufen, or triflusal.
16 . The method of claim 11 , wherein the thromboxane inhibitor is dipyridamole, picotamide, or terutroban.
17 . A method for screening for a drug candidate for the treatment of sepsis comprising the steps of
a. treating a cell sample with an agent;
b. adding granzyme B containing platelets to the treated cell sample; and
b. determining whether the agent is effective in preventing apoptosis of the cells when compared to controlled cells not treated with the compound.
18 . The method of claim 17 , wherein the agent is selected from the group consisting of proteins, peptides, small molecules, vitamin derivatives, and carbohydrates.
19 . The method of claim 17 , further comprising the step determining whether the agent is effective in preventing platelet aggregation.