Retinoid replacements and opsin agonists and methods for the use thereof

• US 20060281821A1
• Filed: 03/15/2004
• Published: 12/14/2006
• Est. Priority Date: 03/14/2003
• Status: Abandoned Application

• Current Assignee: University of Washington
• Original Assignee: University of Washington
• Inventors: Saperstein, David A., Palczewski, Krzysztof
• Application Number:
  US10/548,612
• Publication Number:
  US 20060281821A1
• Time in Patent Office: Days
• US Class Current: 514/703
• CPC Class Codes: A61K 31/07 Retinol compounds, e.g. vitamin A retinoic acids A61K31/203
• CPC Class Codes: A61K 31/11 Aldehydes
• CPC Class Codes: A61K 31/382 having six-membered rings, e.g. thioxanthenes thiothixene A61K31/496
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/695 Silicon compounds
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia

Abstract

Compositions of and methods for using synthetic retinoids as retinoid replacements and opsin agonists are provided.

Claims

1. A method of restoring photoreceptor function in a vertebrate eye, comprising administering to the vertebrate having an endogenous deficiency an effective amount of a synthetic retinoid in a pharmaceutically acceptable vehicle, wherein the synthetic retinoid binds to opsin in the vertebrate eye and forms a functional opsin/synthetic retinoid complex.

2. The method of claim 1, wherein the synthetic retinoid is 9-cis-retinal.

3. The method of claim 1, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

4. The method of claim 1, wherein the endogenous retinoid deficiency is associated with Age-Related Macular Degeneration, Leber Congenital Amaurosis, Retinitis Punctata Albesciens, Congenital Stationary Night Blindness or Fundus Albipunctatus.

5. The method of claim 1, wherein the synthetic retinoid is locally administered to the eye.

6. The method of claim 5, wherein the synthetic retinoid is locally administered by eye drops, intraocular injection or periocular injection.

7. The method of claim 1, wherein the synthetic retinoid is orally administered to the vertebrate.

8. A method of sparing the requirement for endogenous retinoid in a vertebrate eye, comprising:

administering to the eye a synthetic retinoid in a pharmaceutically acceptable vehicle, wherein the synthetic retinoid binds to opsin in the vertebrate eye and forms a functional opsin/synthetic retinoid complex.

9. The method of claim 8, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

10. The method of claim 8, wherein the synthetic retinoid is 9-cis-retinal.

11. The method of claim 8, wherein the endogenous retinoid is 11-cis-retinal.

12. A method of ameliorating loss of photoreceptor function in a vertebrate eye, comprising:

prophylactically administering an effective amount of a synthetic retinoid in a pharmaceutically acceptable vehicle to the vertebrate eye, wherein the synthetic binds to opsin protein to form a functional opsin/synthetic retinoid complex.

13. The method of claim 12, wherein the synthetic retinoid is orally administered to a vertebrate comprising the eye.

14. The method of claim 12, wherein the synthetic retinoid is locally administered to the vertebrate eye.

15. The method of claim 12, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

16. The method of claim 12, wherein the synthetic retinoid is 9-cis-retinal.

17. A method of selecting a treatment for a subject having diminished visual capacity, comprising:

determining whether the subject has a deficient endogenous retinoid level, as compared with a standard subject; and

administering to the subject an effective amount of a synthetic retinoid in a pharmaceutically acceptable vehicle, wherein the synthetic retinoid binds to opsin in the subject'"'"'s eye.

18. The method of claim 17, wherein the subject has Leber Congenital Amaurosis, Retinitis Punctata Albesciens, Congenital Stationary Night Blindness, Fundus Albipunctatus or Age-Related Macular Degeneration.

19. The method of claim 17, wherein the endogenous retinoid is 11-cis-retinal.

20. The method of claim 17, wherein the synthetic retinoid is orally administered to a vertebrate comprising the eye.

21. The method of claim 17, wherein the synthetic retinoid is locally administered to the vertebrate eye.

22. The method of claim 17, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

23. The method of claim 17, wherein the synthetic retinoid is 9-cis-retinal.

24. An ophthalmologic composition comprising a synthetic retinoid in a pharmaceutically acceptable vehicle.

25. The composition of claim 24, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

26. The composition of claim 24, wherein the synthetic retinoid is 9-cis-retinal.

27. The composition of claim 24, wherein the ophthalmologic composition comprises eye drops, an intraocular injectable solution or a periocular injectable solution.

28. An oral dosage form comprising an opsin-binding synthetic retinoid in a pharmaceutically acceptable vehicle.

29. The composition of claim 28, wherein the opsin-binding synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

30. The composition of claim 28, wherein the synthetic retinoid is 9-cis-retinal.

31. A method of treating Leber Congenital Amaurosis in a vertebrate subject, comprising:

administering to the subject an effective amount of a synthetic retinoid in a pharmaceutically acceptable vehicle, wherein the synthetic retinoid binds to opsin in the vertebrate eye and forms a functional opsin/synthetic retinoid complex.

32. The method of claim 31, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

33. The method of claim 31, wherein the synthetic retinoid is 9-cis-retinal.

34. The method of claim 31, wherein the synthetic retinoid is locally administered to the eye.

35. The method of claim 34, wherein the synthetic retinoid is locally administered by eye drops, intraocular injection or periocular injection.

36. The method of claim 31, wherein the synthetic retinoid is orally administered to the subject.

37. A method of treating Retinitis Punctata Albesciens, Congenital Stationary Night Blindness or Fundus Albipunctatus in a vertebrate subject, comprising:

administering to the subject an effective amount of a synthetic retinoid in a pharmaceutically acceptable vehicle, wherein the synthetic retinoid binds to opsin in the vertebrate eye and forms a functional opsin/synthetic retinoid complex.

38. The method of claim 37, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

39. The method of claim 37, wherein the synthetic retinoid is 9-cis-retinal.

40. The method of claim 37, wherein the synthetic retinoid is locally administered to the eye.

41. The method of claim 40, wherein the synthetic retinoid is locally administered by eye drops, intraocular injection or periocular injection.

42. The method of claim 37, wherein the synthetic retinoid is orally administered to the subject.

43. A method of treating Age-Related Macular Degeneration in a vertebrate subject, comprising:

administering to the subject an effective amount of a synthetic retinoid in a pharmaceutically acceptable vehicle, wherein the synthetic retinoid binds to opsin in the vertebrate eye and forms an opsin/synthetic retinoid complex.

44. The method of claim 43, wherein the synthetic retinoid binds to free opsin in the eye.

45. The method of claim 43, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

46. The method of claim 43, wherein the synthetic retinoid is 9-cis-retinal.

47. The method of claim 43, wherein the synthetic retinoid is locally administered to the eye.

48. The method of claim 47, wherein the synthetic retinoid is locally administered by eye drops, intraocular injection or periocular injection.

49. The method of claim 43, wherein the synthetic retinoid is orally administered to the subject.

50. A method of treating or preventing loss of night vision or contrast sensitivity in an aging vertebrate subject, comprising:

administering to the subject an effective amount of a synthetic retinoid in a pharmaceutically acceptable vehicle, wherein the synthetic retinoid binds to opsin in the vertebrate eye and forms an opsin/synthetic retinoid complex.

51. The method of claim 50, wherein the synthetic retinoid binds to free opsin in the eye.

52. The method of claim 50, wherein the synthetic retinoid comprises a synthetic retinoid of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII or XIII.

53. The method of claim 50, wherein the synthetic retinoid is 9-cis-retinal.

54. The method of claim 50, wherein the synthetic retinoid is locally administered to the eye.

55. The method of claim 54, wherein the synthetic retinoid is locally administered by eye drops, intraocular injection or periocular injection.

56. The method of claim 50, wherein the synthetic retinoid is orally administered to the subject.

57. The method of claim 50, wherein the synthetic retinoid is administered prophylactically to the subject.

58. The method of claim 50, wherein the subject is a human.