Modulation of platelet aggregation
View Patent ↗Methods and compositions for inhibition of platelet cell aggregation are described. In particular, compositions comprising cell permeant RGT peptides, such as RGT bound to a lipid moiety are provided. Compositions may be used in the treatment and prevention of clot related diseases such as stroke and myocardial infarction.
1. A composition comprising a peptide consisting of the amino acid sequence RGT and a lipid covalently bound to the amino-terminus of said peptide.
2. The composition of claim 1 , wherein the lipid is a fatty acid.
3. The composition of claim 2 , wherein the fatty acid is a saturated fatty acid.
4. The composition of claim 3 , wherein the saturated fatty acid is a myristic acid or palmitic acid.
5. The composition of claim 4 , wherein the saturated fatty acid is myristic acid.
6. A pharmaceutical composition comprising a composition according to claim 1 in a pharmaceutically acceptable carrier.
7. A method for inhibiting platelet aggregation in a subject comprising administering to the subject the composition of claim 1 , said composition administered in an amount effective to inhibit platelet aggregation.
8. The method of claim 7 , wherein the lipid is a fatty acid.
9. The method of claim 8 , wherein the fatty acid is a saturated fatty acid.
10. The method of claim 9 , wherein the saturated fatty acid is a myristic acid or palmitic acid.
11. The method of claim 9 , wherein the saturated fatty acid is myristic acid.
12. The method of claim 7 , wherein the RGT peptide inhibits or reduces phosphorylation of integrin β3 in a platelet cell.
13. The method according to claim 7 , further comprising administering a therapeutic drug to the subject before, after or concurrently with the composition.
14. The method according to claim 13 , wherein the therapeutic drug is clopidogrel, ticlopidine, cilostazol, abciximab, eptifibatide, tirofiban, defibrotide, dipyridamole or aspirin.
15. The method of claim 7 , wherein the subject has atherosclerosis.
16. The method of claim 7 , wherein, the composition is administered to the subject by oral, nasal, topical, orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal or intravenous administration.
17. The method of claim 16 , wherein the composition administered to a subject by intravenous administration.
18. The method of claim 7 , wherein the composition further comprises a pharmaceutically acceptable carrier.
19. A method for reducing the occurrence of a secondary ischemic event in a subject comprising administering to a subject who has suffered a primary ischemic event a therapeutically effective amount of the composition of claim 1 .
20. The method of claim 19 , wherein the primary and/or secondary ischemic event is angina, reocclusion after percutaneous transluminal coronary angioplasty, restenosis, thrombotic stroke, transient ischemic attack, reversible ischemic neurological deficit or intermittent claudication.
21. A method for reducing the size of a blood clot in a subject comprising administering to the subject the composition of claim 1 , said composition administered in an amount effective to reduce the size of a blood clot.
22. The method of claim 21 , wherein the lipid is a fatty acid.
23. The method of claim 22 , wherein the fatty acid is a saturated fatty acid.
24. The method of claim 22 , wherein the saturated fatty acid is a myristic acid or palmitic acid.
25. The method of claim 24 , wherein the saturated fatty acid is myristic acid.
26. The method of claim 21 , wherein the RGT amino acid sequence inhibits or reduces phosphorylation of integrin β3 in a platelet cell.
27. The method according to claim 21 , further comprising administering a therapeutic drug to the subject before, after or concurrently with the composition.
28. The method according to claim 27 , wherein the therapeutic drug is an anticoagulant.
29. The method according to claim 28 , wherein the anticoagulant is warfarin, acenocoumarol, phenprocoumon, phenindione, heparin, fondaparinux, idraparinux, argatroban, lepirudin, bivalirudin or dabigatran.
30. The method according to claim 27 , wherein the therapeutic drug is a thrombolytic drug.
31. The method according to claim 30 , wherein the thrombolytic drug is streptokinase, tissue plasminogen activator (tPA), urokinase, Reteplase, tenecteplase, anistreplase or brinase.
32. The method of claim 21 , wherein, the composition is administered to the subject by oral, nasal, topical, orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal or intravenous administration.
33. The method of claim 32 , wherein the composition is administered to the subject by intravenous administration.
34. The method of claim 21 , wherein the composition further comprises a pharmaceutically acceptable carrier.
35. The method of claim 21 , wherein the subject has pulmonary embolism, venous thrombosis, deep vein thrombosis, portal vein thrombosis, renal vein thrombosis, jugular vein thrombosis, Budd-Chiari syndrome, Paget-Schroetter disease, cerebral venous sinus thrombosis, arterial thrombosis, thrombotic stroke or myocardial infarction.