Oxidative retinal diseases
Some aspects of the invention provide for a method of treating Wet and/or Dry Age-related Macular Degeneration, Retinitis Pigmentosa, Diabetic Retinopathy, cataracts, and/or Stargardt Disease using polyunsaturated fatty acids which are modified in certain positions to attenuate oxidative damage by Reactive Oxygen Species (ROS) and/or suppress the rate of formation of reactive products and toxic compounds.
1. A method of treating or inhibiting progression of an oxidative retinal disease selected from the group consisting of Age-related Macular Degeneration, Retinitis Pigmentosa, Diabetic Retinopathy, and Stargardt Disease, comprising:
repeatedly administering an effective amount of a deuterated polyunsaturated fatty acid or fatty acid ester to a patient wherein the polyunsatruated fatty acid or fatty acid ester is deuterated at one or more bis-allylic positions;
wherein the amount of deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient is in the range of about 1% to about 99% of the total amount of polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient, and wherein over the treatment period a significant amount of deuterated polyunsaturated fatty acid or fatty acid ester is incorporated into the patient's eyes such that the amount of deuterated polyunsaturated fatty acid or fatty acid ester is sufficient to reduce or prevent autoxidation and cancel toxicity of undeuterated polyunsaturated fatty acid or fatty acid ester in the patient's eyes; and
wherein the deuterated polyunsaturated fatty acid or fatty acid ester is arachidonic acid, an arachidonic acid ester, eicosapentaenoic acid, an eicosapentaenoic acid ester, docosahexaenoic acid, a docosahexaenoic acid ester, linoleic acid, a linoleic acid ester, linolenic acid, or a linolenic acid ester.
2. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is deuterated at a level greater than 0.02%.
3. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient comprises between about 1% and 50% of the total amount of fatty acids or fatty acid esters in the patient's eye.
4. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient comprises between about 1% and 30% of the total amount of fatty acids or fatty acid esters in the patient's eye.
5. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient comprises between about 20% and 50% of the total amount of fatty acids or fatty acid esters in the patient's eye.
6. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is arachidonic acid.
7. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is an arachidonic acid ester.
8. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is docosahexaenoic acid.
9. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is a docosahexaenoic acid ester.
10. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is linoleic acid.
11. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is a linoleic acid ester.
12. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is linolenic acid.
13. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is a linolenic acid ester.
14. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is selected from the group consisting of 11,11-D2-linolenic acid, 14,14-D2-linolenic acid, 11,11,14,14-D4-linolenic acid, 11,11-D2-linoleic acid, 11-D-linolenic acid, 14-D-linolenic acid, 11,14-D2-linolenic acid, and 11-D-linoleic acid.
15. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is selected from the group consisting of a 11,11-D2-linolenic acid ester, a 14,14-D2-linolenic acid ester, a 11,11,14,14-D4-linolenic acid ester, a 11,11-D2-linoleic acid ester, a 11-D-linolenic acid ester, a 14-D-linolenic acid ester, a 11,14-D2-linolenic acid ester, and a 11-D-linoleic acid ester.
16. The method of claim 1 , wherein the ester is a triglyceride, diglyceride, or monoglyceride.
17. The method of claim 1 further comprising co-administering an antioxidant.
18. The method of claim 17 , wherein the antioxidant is idebenone, mitoquinone, mitoquinol, vitamin C, or vitamin E.
19. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is administered topically to the patient's eye.
20. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is administered orally.
21. The method of claim 1 , wherein the amount of deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient is in the range of about 0.1 mg/kg to 100 mg/kg per day.
22. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11-D2-linoleic acid.
23. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11-D2-linoleic acid ethyl ester.
24. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,1114,14-D4-linolenic acid.
25. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11,14,14-D4-linolenic acid ethyl ester.