Use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization

• US 7,517,870 B2
• Filed: 12/03/2004
• Issued: 04/14/2009
• Est. Priority Date: 12/03/2004
• Status: Expired due to Fees

• Current Assignee: Fondazione Telethon
• Original Assignee: Fondazione Telethon
• Inventors: Hildinger, Markus, Auricchio, Alberto, Surace, Enrico Maria
• Primary Examiner(s): Fetterolf; Brandon J
• Application Number:
  US11/002,882
• Publication Number:
  US 20060276391A1
• Time in Patent Office: 1,593 Days
• Field of Search: None
• US Class Current: 514/176
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4355 the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector

Abstract

The present invention concerns the use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization. Particularly, the above-mentioned diseases are (wet) age-related macular degeneration, (proliferative) diabetic retinopathy, neovascular glaucoma, retinal vein occlusion, or retinopathy of prematurity (ROP).

Claims

1. A method inhibiting and/or reversing a disease related with ocular neovascularization in a mammalian subject comprising administering to the subject a therapeutically effective amount of a soluble Hedgehog interacting protein 1 (Hip1) consisting of the amino acids of SEQ ID NO:

6 obtained from Hip1 by deletion of the transmembrane segment located at the C-terminus, and optionally containing a signal peptide.

2. The method according to claim 1, wherein the disease is selected from the group consisting of age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity (ROP), neovascular glaucoma, and retinal vein occlusion.

11. The method according to claim 1, wherein said soluble Hip1 has a signal peptide.

3. A method of inhibiting and/or reversing ocular neovascularization diseases in a mammalian subject comprising administering to the subject a therapeutically effective amount of soluble Hedgehog interacting protein 1 (Hip1) consisting of the amino acids of SEQ ID NO:

6 wherein said soluble Hip1 binds to and sequesters Hedgehog protein to interfere with Hedgehog signaling.

4. The method according to claim 3, wherein the disease is selected from the group consisting of age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity (ROP), neovascular glaucoma, and retinal vein occlusion.

5. The method according to claim 3, wherein the disease is selected from the group consisting of age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion.

6. The method according to claim 4, wherein the disease is an age-related macular degeneration.

7. The method according to claim 3, wherein the disease is diabetic retinopathy.

8. The method according to claim 4, wherein the disease is retinopathy of prematurity (ROP).

9. The method according to claim 3, wherein the disease is neovascular glaucoma.

10. The method according to claim 3, wherein the disease is retinal vein occlusion.

12. The method according to claim 3, wherein said soluble Hip1 has a signal peptide.