Therapeutic regimen and methods for treating or ameliorating visual disorders associated with an endogenous retinoid deficiency
Disclosed herein are therapeutic regimens for treating or ameliorating a visual disorder associate with an endogenous retinoid deficiency in a subject by administering a therapeutically effective amount of a synthetic retinal derivative or a pharmaceutically acceptable composition comprising a synthetic retinal derivative according to the therapeutic regimen which leads to local recovery of visual functions such as visual fields, visual acuity and retinal sensitivity, among others.
1. A method for treating a human patient suffering from the loss or impairment of vision caused by Leber Congenital Amaurosis (LCA), wherein said patient is deficient in endogenous 11-cis-retinal disorder, comprising the steps of:
a) administering to the human patient an initial therapeutically effective dose of a synthetic retinal derivative selected from the group consisting of 9-cis-retinyl acetate, 9-cis-retinyl formate, 9-cis-retinyl succinate, 9-cis-retinyl citrate, 9-cis-retinyl ketoglutarate, 9-cis-retinyl fumarate, 9-cis-retinyl malate, 9-cis-retinyl oxaloacetate, 9-cis-retinyl propionate, 9-cis-retinyl butyrate, 9-cis-retinyl valerate, 9-cis-retinyl hexanoate, 9-cis-retinyl heptanoate, 9-cis-retinyl octanoate, 9-cis-retinyl nonanoate, 9-cis-retinyl decanoate, 9-cis-retinyl undecanoate, 9-cis-retinyl dodecanoate, 9-cis-retinyl oxalate, 9-cis-retinyl malonate, 9-cis-retinyl glutarate, 9-cis-retinyl adipate, 9-cis-retinyl pimelate, 9-cis-retinyl suberate, 9-cis-retinyl azelate, and 9-cis-retinyl sebacate,
b) refraining from administering to the human patient an additional therapeutically effective dose of the synthetic retinal derivative for a resting interval, wherein the resting interval is a time period between 1 month and 14 months,
c) administering to the human patient the additional therapeutically effective dose of the synthetic retinal derivative.
2. The method of claim 1 , wherein the initial dose is administered in a single dose.
3. The method of claim 1 , wherein the initial dose is administered in a divided dose over a period of from 5 to 14 days.
4. The method of claim 1 , wherein the initial dose is administered in a divided dose over a period of 7 to 10 days.
5. The method of claim 1 , wherein the initial dose is administered in a divided dose over a period of one week.
6. The method of claim 1 , wherein the synthetic retinal derivative is 9-cis-retinyl acetate.
7. The method of claim 6 , wherein the initial dose is administered in a divided dose over a period of two weeks.
8. The method of claim 1 , wherein the initial dose is in the range of from 70 mg/m 2 to 525 mg/m 2 .
9. The method of claim 1 , wherein the initial dose is in the range of from 70 mg/m 2 to 490 mg/m 2 .
10. The method of claim 1 , wherein the initial dose is in the range of from 280 mg/m 2 to 490 mg/m 2 .
11. The method of claim 1 , wherein the initial dose is in the range of from 70 mg/m 2 to 280 mg/m 2 .
12. The method of claim 5 , wherein the initial dose is 280 mg/m 2 .
13. The method of claim 8 , wherein the initial dose of a synthetic retinal derivative is administered orally.
14. The method of claim 8 , wherein the initial dose of a synthetic retinal derivative is administered by intraocular injection.
15. The method of claim 1 , wherein the resting interval is a time period between 3 months and 14 months.
16. The method of claim 15 , wherein the resting interval is a time period between 6 months and 14 months.
17. The method of claim 15 , wherein the resting interval is a time period between 9 months and 14 months.
18. The method of claim 15 , wherein the resting interval is a time period between 3 and 6 months.
19. The method of claim 15 , wherein the resting interval is a time period between 6 and 9 months.
20. The method of claim 15 , wherein the resting interval is a time period between 3 and 9 months.
21. The method of claim 15 , wherein the resting interval is a time period between 3 months and 1 year.
22. The method of claim 1 , wherein the LCA is caused by a mutation in the LRAT gene.
23. The method of claim 1 , wherein the LCA is caused by a mutation in the RPE65 gene.
24. A method for treating a human patient suffering from loss or impairment of vision due to inherited mutations in RPE65 or LRAT genes associated with Leber congenital amaurosis, comprising the steps of:
a) administering to the human patient an initial therapeutically effective dose of 9-cis-retinyl acetate,
b) refraining from administering to the human patient an additional therapeutically effective dose of the 9-cis-retinyl acetate for a resting interval, wherein the resting interval is a time period between 1 month and 14 months, and
c) administering to the human patient the additional therapeutically effective dose of the 9-cis-retinyl acetate.
25. The method of claim 24 , wherein the initial dose is administered in a divided dose over a period of from 5 to 14 days.
26. The method of claim 24 , wherein the initial dose is in the range of from 70 mg/m 2 to 525 mg/m 2 .
27. The method of claim 24 , wherein the resting interval is a time period between 3 months and 14 months.
28. The method of claim 1 , wherein the resting interval is a time period between 1 month and 2 months.
29. The method of claim 1 , wherein the resting interval is a time period between 1 month and 3 months.
30. The method of claim 1 , wherein the resting interval is a time period between 1 month and 6 months.
31. The method of claim 1 , wherein the resting interval is a time period between 1 month and 9 months.
32. The method of claim 1 , wherein the resting interval is a time period between 1 month and 1 year.
33. The method of claim 24 , wherein the resting interval is a time period between 1 month and 2 months.
34. The method of claim 24 , wherein the resting interval is a time period between 1 month and 3 months.
35. The method of claim 24 , wherein the resting interval is a time period between 1 month and 6 months.
36. The method of claim 24 , wherein the resting interval is a time period between 1 month and 9 months.
37. The method of claim 24 , wherein the resting interval is a time period between 1 month and 1 year.
38. The method of claim 24 , wherein the resting interval is a time period between 6 months and 14 months.
39. The method of claim 24 , wherein the resting interval is a time period between 9 months and 14 months.
40. The method of claim 24 , wherein the resting interval is a time period between 3 months and 6 months.
41. The method of claim 24 , wherein the resting interval is a time period between 6 months and 9 months.
42. The method of claim 24 , wherein the resting interval is a time period between 3 months and 9 months.
43. The method of claim 24 , wherein the resting interval is a time period between 3 months and 1 year.
44. The method of claim 1 , wherein the initial dose is in the range of from 49 mg/m 2 to 840 mg/m 2 .
45. The method of claim 44 , wherein the initial dose is in the range of from 49 mg/m 2 to 280 mg/m 2 .
46. The method of claim 24 , wherein the initial dose is in the range of from 49 mg/m 2 to 840 mg/m 2 .
47. The method of claim 46 , wherein the initial dose is in the range of from 49 mg/m 2 to 280 mg/m 2 .