Treatment of fibrotic conditions
Treatment of fibrosis and fibrotic diseases, disorders, and conditions, and associated methods, compositions, formulations and articles.
1. A method of preventing or decreasing fibrosis of the eye in a subject in need thereof, the method comprising administering to the eye of said subject an anti-connexin 43 antisense polynucleotide.
2. The method of claim 1 , wherein said anti-connexin polynucleotide is an antisense polynucleotide selected from the group consisting of unmodified and chemically modified antisense deoxyoligonucleotides.
3. The method of claim 1 , wherein the anti-connexin polynucleotide is administered to prevent or retard fibrosis.
4. The method of claim 1 , wherein the subject has fibrotic macular degeneration.
5. The method of claim 1 , wherein the antisense polynucleotide comprises a nucleobase sequence selected from SEQ ID Nos: 1 and 2.
6. The method of claim 1 , wherein the anti-connexin polynucleotide is targeted to at least about 8 nucleobases of a nucleic acid molecule encoding connexin 43.
7. The method of claim 6 , wherein the anti-connexin 43 antisense polynucleotide is an antisense oligonucleotide of between about 15 and about 35 nucleobases in length.
8. The method of claim 1 , wherein the anti-connexin 43 antisense polynucleotide is targeted to at least about 12 nucleobases of a nucleic acid molecule encoding a connexin.
9. The method of claim 1 , wherein the anti-connexin 43 antisense polynucleotide is an antisense oligonucleotide comprising naturally occurring nucleobases and an unmodified internucleoside linkage.
10. The method of claim 1 , wherein the anti-connexin 43 antisense polynucleotide is an antisense oligonucleotide comprising at least one modified internucleoside linkage.
11. The method of claim 10 , wherein the modified internucleoside linkage is a phosphorothioate linkage.
12. The method of claim 1 , wherein the anti-connexin 43 antisense polynucleotide is an oligonucleotide comprising at least one modified sugar moiety.
13. The method of claim 1 , wherein the anti-connexin 43 antisense polynucleotide is an oligonucleotide comprising at least one modified nucleobase.
14. A method of claim 1 , wherein said anti-connexin 43 antisense polynucleotide is administered in combination with a second compound useful for reducing tissue damage or promoting healing.
15. A method of claim 14 , wherein the second compound is a growth factor or cytokine.
16. A method of claim 14 , wherein the second compound is an antagonist of VEGF or pro-inflammatory cytokines.
17. A method of claim 1 - 4 or 5 , wherein said anti-connexin 43 antisense polynucleotide is administered in single or divided applications.
18. A method of claim 1 - 4 or 5 , wherein the administration of said anti-connexin 43 antisense polynucleotide is repeated weekly.
19. A method of claim 1 - 4 or 5 , wherein the administration of said anti-connexin 43 antisense polynucleotide is bi-weekly, monthly.
20. A method of claim 1 - 4 or 5 , wherein said anti-connexin 43 antisense polynucleotide is administered topically.
21. A method of claim 1 - 4 or 5 , wherein said anti-connexin 43 antisense polynucleotide is implanted or instilled or injected.
22. A method of claim 1 - 4 or 5 , wherein said anti-connexin 43 antisense polynucleotide is administered in a sustained- or slow-release formulation.
23. A method of claim 1 - 4 or 5 , wherein said anti-connexin 43 antisense polynucleotide is administered as a gel.
24. A method of claim 23 , wherein said gel is a nonionic polyoxyethylene-polyoxypropylene copolymer gel.
25. A method of claim 23 , wherein said gel is a Pluronic gel.
26. A method of claim 23 , wherein said gel is Pluronic F-127.