Compositions and methods for treating retinal degradation

Patent metadata

Field	Value
Publication number	US-9326983-B2
Application number	US-201414450000-A
Country	US
Kind code	B2
Filing date	Aug 1, 2014
Priority date	Aug 1, 2013
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.

First claim

What is claimed is:

1. A method for treating retinal degeneration, comprising:
administering an effective amount of a composition to a subject in need of treatment for retinal degeneration,
wherein the composition comprises a reverse transcriptase inhibitor selected from:
(i) a compound having the structure of

 or a pharmaceutically acceptable salt thereof;
(ii) a compound having the structure of

 or a pharmaceutically acceptable salt thereof;
(iii) stavudine (d4T);
(iv) lamivudine (3TC);
(v) cordycepin;
(vi) azidothymidine (AZT);
(vii) abacavir (ABC); and
(viii) a combination thereof.

2. The method of claim 1 , comprising inhibiting inflammasome activation by Alu RNA associated with a cell.

3. The method of claim 2 , wherein the cell is a retinal pigmented epithelium cell, a retinal photoreceptor cell, a choroidal cell, or a combination thereof.

4. The method of claim 1 , comprising reducing ATP-induced permeability of a cell.

5. The method of claim 4 , wherein the cell is a retinal pigmented epithelium cell, a retinal photoreceptor cell, a choroidal cell, or a combination thereof.

6. The method of claim 1 , comprising reducing an amount of mitochondrial reactive oxygen species in a cell.

7. The method of claim 1 , comprising inhibiting activation of at least one inflammasome in a subject's eye.

8. The method of claim 7 , wherein the at least one inflammasome is selected from an NLRP3 inflammasome, an IL-1 beta inflammasome, and a combination thereof.

9. The method of claim 1 , wherein the composition comprises a pharmaceutically acceptable carrier.

10. A compound having the structure

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising the compound of claim 10 and a pharmaceutically acceptable carrier.

12. A compound having the structure

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising the compound of claim 12 and a pharmaceutically acceptable carrier.

14. A method for treating retinal degeneration, comprising:
administering an effective amount of a composition to a subject in need of treatment for retinal degeneration,
wherein the composition comprises:
(i) a compound having the structure of

 or a pharmaceutically acceptable salt thereof; or
(ii) a compound having the structure of

 or a pharmaceutically acceptable salt thereof.

15. The method of claim 14 , wherein the composition further comprises: stavudine (d4T), lamivudine (3TC), cordycepin, azidothymidine (AZT), abacavir (ABC), or a combination thereof.

16. The method of claim 14 , comprising inhibiting inflammasome activation by Alu RNA associated with a cell.

17. The method of claim 16 , wherein the cell is a retinal pigmented epithelium cell, a retinal photoreceptor cell, a choroidal cell, or a combination thereof.

18. The method of claim 14 , comprising reducing ATP-induced permeability of a cell.

19. The method of claim 18 , wherein the cell is a retinal pigmented epithelium cell, a retinal photoreceptor cell, a choroidal cell, or a combination thereof.

20. The method of claim 14 , comprising reducing an amount of mitochondrial reactive oxygen species in a cell.

21. The method of claim 14 , comprising inhibiting activation of at least one inflammasome in a subject's eye.

22. The method of claim 21 , wherein the at least one inflammasome is selected from an NLRP3 inflammasome, an IL-1 beta inflammasome, and a combination thereof.

23. The method of claim 14 , wherein the composition comprises a pharmaceutically acceptable carrier.

Assignees

• Univ Kentucky Res Found

Inventors

• Ambati Jayakrishna
• Fowler Benjamin

Classifications

• A61K31/513 Primary

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K31/7052

  having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides · CPC title

• A61K31/7072

  having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title