Peptide therapies for reduction of macular thickening
Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH 2 —SO 3 H)COOH or Arg-Gly-NH—CH(CH 2 —SO 3 H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting integrins including but not necessarily limited to α 5 β 1 -Integrin, α v β 3 -Integrin and α v β 5 -Integrin, inhibiting cellular adhesion to RGD binding sites, preventing or treating viral or other microbial infections, inhibiting angiogenesis in tumors, retinal tissue or other tissues or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.
1. A method for treating pathological thickening of the macula of an eye in a subject in need thereof, said method comprising administering to the subject a pharmaceutical composition comprising either:
i) a peptide which comprises Glycinyl-Arginyl-Glycinyl-Cysteic Acid-Threonyl-Proline-COOH (SEQ ID NO. 2); or
ii) a peptide having the general formula (SEQ ID NO 9):
X1-R-G-Cysteic Acid-X
where X and X1 are each independently selected from: Phe-Val-Ala, Phe-Leu-Ala, Phe-Val-Gly, Phe-Leu-Gly, Phe-Pro-Gly, Phe-Pro-Ala, Phe-Val, or any salt or any combination of the D-isomer or L-isomer thereof.
2. A method according to claim 1 wherein the peptide inhibits at least α5β1-Integrin, αvβ3-Integrin and αvβ5-Integrin.
3. A method according to claim 1 herein the peptide inhibits an Integrin associated with a cell adhesion motif.
4. A method according to claim 3 wherein the peptide inhibits an integrin associated with fibronectin, vitronectin, laminin, fibrinogen, thrombospondin, and von Willebrand factor.
5. A method according to claim 1 wherein the composition is administered by intravitreal injection.
6. A method according to claim 1 wherein the peptide comprises a linear form of Glycinyl-Arginyl-Glycinyl-Cysteic Acid-Threonyl-Proline-COOH (SEQ ID NO 2).
7. A method according to claim 1 wherein the peptide comprises a cyclic form of Glycinyl-Arginyl-Glycinyl-Cysteic Acid-Threonyl-Proline-COOH (SEQ ID NO 2).
8. A method according to claim 1 wherein the subject suffers from macular edema.
9. A method according to claim 8 wherein the subject suffers from diabetic macular edema.
10. A method according to claim 6 wherein the peptide has the structural formula:
11. A method according to claim 6 wherein the peptide is administered intraviterally.
12. A method according to claim 11 wherein the peptide is administered by intravitreal injection of a solution that contains the peptide.
13. A method according to claim 12 wherein the intravitreal injection is repeated.
14. A method according to claim 13 wherein the intravitreal injection is repeated monthly.
15. A method according to claim 12 wherein the intravitreal injection delivers 2.5 mg of the peptide.