Treatment of leber's hereditary optic neuropathy and dominant optic atrophy with tocotrienol quinones
The present invention relates to methods of treating Leber's hereditary optic neuropathy and dominant optic atrophy with tocotrienol quinones, including alpha-tocotrienol quinone, in order to alleviate symptoms of the disease.
1. A method of treating a disease in a symptomatic patient with a mutation in an OPA gene, comprising administering a therapeutically effective amount of a compound selected from the group consisting of tocotrienol quinones and tocotrienol hydroquinones.
2. The method of claim 1 , wherein the compound is selected from the group consisting of alpha-tocotrienol quinone, beta-tocotrienol quinone, gamma-tocotrienol quinone, and delta-tocotrienol quinone.
3. The method of claim 1 , wherein the compound is selected from the group consisting of alpha-tocotrienol hydroquinone, beta-tocotrienol hydroquinone, gamma-tocotrienol hydroquinone, and delta-tocotrienol hydroquinone.
4. The method of claim 2 , wherein the compound is alpha-tocotrienol quinone.
5. The method of claim 1 , wherein the OPA gene is OPA1.
6. The method of claim 1 , wherein the patient has one or more symptoms selected from the group consisting of: loss of visual acuity, loss of central vision, impairment of color vision, centrocecal scotomas, temporal pallor of the optic disc, circumpapillary telangiectatic microangiopathy, sparing of pupillary light responses, swelling of the retinal nerve fiber layer around the disc (pseudoedema), and optic atrophy.
7. The method of claim 4 , comprising administering a pharmaceutical preparation containing from about 50 mg to about 500 mg of alpha-tocotrienol quinone.
8. The method of claim 4 , comprising administering a pharmaceutical preparation containing sufficient alpha-tocotrienol quinone to provide a therapeutic level of compound in at least the retina or the optic nerve system of the patient.
9. The method of claim 1 , wherein the alpha-tocotrienol quinone comprises at least about 50% by weight of the tocotrienols and tocotrienol quinones present in the preparation.
10. The method of claim 9 , wherein the alpha-tocotrienol quinone comprises at least about 80% by weight of the material present in the preparation, excluding the weight of any added pharmaceutical carriers or excipients.
11. The method of claim 4 , comprising administering the alpha-tocotrienol quinone as a unit dosage formulation of alpha-tocotrienol quinone, wherein the alpha-tocotrienol quinone comprises at least about 95% by weight of the tocotrienols and tocotrienol quinones present in the unit dosage formulation.
12. The method of claim 11 , wherein the alpha-tocotrienol quinone comprises at least about 95% by weight of the material present in the unit dosage formulation, excluding the weight of any pharmaceutical carriers or excipients.
13. The method of claim 9 , wherein the patient has one or more symptoms selected from the group consisting of: loss of visual acuity, loss of central vision, impairment of color vision, centrocecal scotomas, temporal pallor of the optic disc, circumpapillary telangiectatic microangiopathy, sparing of pupillary light responses, swelling of the retinal nerve fiber layer around the disc (pseudoedema), and optic atrophy.
14. The method of claim 9 , wherein the preparation is administered via topical, periocular, or intraocular administration.
15. The method of claim 9 , wherein the preparation is administered via oral administration.
16. The method of claim 1 , wherein the OPA gene is OPA2.
17. The method of claim 1 , wherein the OPA gene is OPA3.
18. The method of claim 1 , wherein the OPA gene is OPA4.
19. The method of claim 1 , wherein the OPA gene is OPA5.
20. The method of claim 1 , wherein the OPA gene is OPA6.
21. The method of claim 1 , wherein the OPA gene is OPA7.
22. The method of claim 3 , wherein the compound is alpha-tocotrienol hydroquinone.