Methods of Treatment of Retinal Degeneration Diseases

• US 20140199277A1
• Filed: 08/06/2012
• Published: 07/17/2014
• Est. Priority Date: 08/05/2011
• Status: Abandoned Application

• Current Assignee: Daniela Sanges, Maria Pia Cosma
• Original Assignee: Daniela Sanges, Maria Pia Cosma
• Inventors: Cosma, Maria Pia, Sanges, Daniela
• Application Number:
  US14/237,297
• Publication Number:
  US 20140199277A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 35/20 Milk; Whey; Colostrum
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: C12N 2501/415 Wnt; Frizzeled
• CPC Class Codes: C12N 5/0606 Pluripotent embryonic cells, e.g. embryonic stem cells [ES] embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0623 Stem cells
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

The methods comprise administering cells having properties of stem cells or progenitor cells, to the retina and reprogramming of retinal cells mediated by cell fusion of said cells with said retinal cells, said reprogramming being mediated by activation of the Wnt/β-catenin signalling pathway.

Claims

1. A cell selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, and a mesenchymal stem cell (MSC), wherein the Wnt/β

-catenin signalling pathway of said cell is activated, for use in the treatment of a retinal degeneration disease.

2. Cell for use in the treatment of a retinal degeneration disease according to claim 1, wherein said cell is a cell treated with a Wnt/β

-catenin signalling pathway activator, or with an inhibitor of a Wnt/β

-catenin signalling pathway repressor, and/or is a cell that overexpresses a Wnt/β

-catenin signalling pathway activator.

3. Cell for use in the treatment of a retinal degeneration disease according to claim 2, wherein said Wnt/β

-catenin pathway activator is selected from the group consisting of a Wnt isoform, β

-catenin, a R-spondin, 2-(4-acetylphenylazo)-2-(3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-ylidene)-acetamide (IQ1), (2S)-2-[2-(indan-5-yloxy)-9-(1,1′

-biphenyl-4-yl)methyl)-9H-purin-6-ylamino]-3-phenyl-propan-1-ol (QS11), deoxycholic acid (DCA), 2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, an (hetero)arylpyrimidine of formula (I), (II), (III) or (IV) shown in Table 1, and combinations thereof.

4. Cell for use in the treatment of a retinal degeneration disease according to claim 2, wherein said inhibitor of a Wnt/β

-catenin pathway repressor is selected from the group consisting of a GSK-3 inhibitor, a SFRP1 inhibitor, and combinations thereof.

5. Cell for use in the treatment of a retinal degeneration disease according to any one of claims 1 to 4, wherein said retinal degeneration disease is selected from the group consisting of retinitis pigmentosa, age-related macular degeneration, Stargardt disease, cone-rod dystrophy, congenital stationary night blindness, Leber congenital amaurosis, Best'"'"'s vitelliform macular dystrophy, anterior ischemic optic neuropathy, choroideremia, age-related macular degeneration, foveomacular dystrophy, Bietti crystalline corneoretinal dystrophy, Usher syndrome, and a retinal degenerative condition derived from a primary pathology.

6. Cell for use in the treatment of a retinal degeneration disease according to claim 5, wherein said retinal degeneration derives from cataracts, diabetes or glaucoma.

7. A cell population comprising a plurality of cells, said cells being selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, a mesenchymal stem cell (MSC) and any combination thereof, wherein the Wnt/β

-catenin signalling pathway of said cells is activated, for use in the treatment of a retinal degeneration disease.

8. Cell population for use in the treatment of a retinal degeneration disease according to claim 7, wherein said cells are cells treated with a Wnt/β

-catenin signalling pathway activator, or with an inhibitor of a Wnt/β

-catenin signalling pathway repressor, and/or are cells that overexpress a Wnt/β

-catenin signalling pathway activator.

9. Cell population for use in the treatment of a retinal degeneration disease according to claim 8, wherein said Wnt/β

-catenin pathway activator is selected from the group consisting of a Wnt isoform, β

-catenin, a R-spondin, IQ 1, QS 11, DCA, 2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl) pyrimidine, an (hetero)arylpyrimidine of formula (I), (II), (III) or (IV) shown in Table 1, and combinations thereof.

10. Cell population for use in the treatment of a retinal degeneration disease according to claim 8, wherein said inhibitor of a Wnt/β

-catenin pathway repressor is selected from the group consisting of a GSK-3 inhibitor, a SFRP1 inhibitor, and combinations thereof.

11. Cell population for use in the treatment of a retinal degeneration disease according to any one of claims 7 to 10, wherein said retinal degeneration disease is selected from the group consisting of retinitis pigmentosa, age-related macular degeneration, Stargardt disease, cone-rod dystrophy, congenital stationary night blindness, Leber congenital amaurosis, Best'"'"'s vitelliform macular dystrophy, anterior ischemic optic neuropathy, choroideremia, age-related macular degeneration, foveomacular dystrophy, Bietti crystalline corneoretinal dystrophy, Usher syndrome, and a retinal degenerative condition derived from a primary pathology.

12. Cell population for use in the treatment of a retinal degeneration disease according to claim 11, wherein said retinal degeneration derives from cataracts, diabetes or glaucoma.

13. A cell selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, and a mesenchymal stem cell (MSC), for use in the treatment of a retinal degeneration disease, by reprogramming, mediated by the Wnt/β

-catenin signalling pathway, of a retinal cell by fusion of said cell with said retinal cell upon contact of said cell and retinal neuron in the eye of a subject.

14. Cell for use in the treatment of a retinal degeneration disease according to claim 13, in combination with a Wnt/β

-catenin signalling pathway activator, or with an inhibitor of a Wnt/β

-catenin signalling pathway repressor.

15. Cell for use in the treatment of a retinal degeneration disease according to claim 14, wherein said Wnt/β

-catenin pathway activator is selected from the group consisting of a Wnt isoform, β

-catenin, a R-spondin, IQ1, QS11, DCA, 2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl) pyrimidine, an (hetero)arylpyrimidine of formula (I), (II), (III) or (IV) shown in Table 1, and combinations thereof.

16. Cell for use in the treatment of a retinal degeneration disease according to claim 14, wherein said inhibitor of a Wnt/β

-catenin pathway repressor is selected from the group consisting of a GSK-3 inhibitor, a SFRP1 inhibitor, and combinations thereof.

17. Cell for use in the treatment of a retinal degeneration disease according to any one of claims 13 to 16, wherein said retinal degeneration disease is selected from the group consisting of retinitis pigmentosa, age-related macular degeneration, Stargardt disease, cone-rod dystrophy, congenital stationary night blindness, Leber congenital amaurosis, Best'"'"'s vitelliform macular dystrophy, anterior ischemic optic neuropathy, choroideremia, age-related macular degeneration, foveomacular dystrophy, Bietti crystalline corneoretinal dystrophy, Usher syndrome, and a retinal degenerative condition derived from a primary pathology.

18. Cell for use in the treatment of a retinal degeneration disease according to claim 17, wherein said retinal degeneration derives from cataracts, diabetes or glaucoma.

19. A cell population comprising a plurality of cells, said cells being selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, a mesenchymal stem cell (MSC) and any combination thereof, for use in the treatment of a retinal degeneration disease, by reprogramming, mediated by the Wnt/β

-catenin signalling pathway, of a retinal cell by fusion of said cell with said retinal cell upon contact of said cell and said retinal cell in the eye of a subject.

20. Cell population for use in the treatment of a retinal degeneration disease according to claim 19, in combination with a Wnt/β

-catenin signalling pathway activator, or with an inhibitor of a Wnt/β

-catenin signalling pathway repressor.

21. Cell population for use in the treatment of a retinal degeneration disease according to claim 20, wherein said Wnt/β

-catenin pathway activator is selected from the group consisting of a Wnt isoform, β

-catenin, a R-spondin, IQ1, QS11, DCA, 2-amino-4-[3,4-(methylenedioxy)benzyl amino]-6-(3-methoxyphenyl) pyrimidine, an (hetero)arylpyrimidine of formula (I), (II), (III) or (IV) shown in Table 1, and combinations thereof.

22. Cell population for use in the treatment of a retinal degeneration disease according to claim 20, wherein said inhibitor of a Wnt/β

-catenin pathway repressor is selected from the group consisting of a GSK-3 inhibitor, a SFRP1 inhibitor, and combinations thereof.

23. Cell population for use in the treatment of a retinal degeneration disease according to any one of claims 19 to 22, wherein said retinal degeneration disease is selected from the group consisting of retinitis pigmentosa, age-related macular degeneration, Stargardt disease, cone-rod dystrophy, congenital stationary night blindness, Leber congenital amaurosis, Best'"'"'s vitelliform macular dystrophy, anterior ischemic optic neuropathy, choroideremia, age-related macular degeneration, foveomacular dystrophy, Bietti crystalline corneoretinal dystrophy, Usher syndrome, and a retinal degenerative condition derived from a primary pathology.

24. Cell population for use in the treatment of a retinal degeneration disease according to claim 23, wherein said retinal degeneration derives from cataracts, diabetes or glaucoma.

25. A cell composition, wherein at least 50% of the cells of said cell composition are selected from the group consisting of hematopoietic stem cells (HSCs), progenitor cells, mesenchymal stem cells (MSCs) and any combination thereof and wherein the Wnt/β

-catenin signalling pathway of said cells is activated.

26. A pharmaceutical composition selected from the group consisting of:

1) a pharmaceutical composition comprising at least a cell selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, a mesenchymal stem cell (MSC), and any combination thereof, wherein the Wnt/β

-catenin signalling pathway of said cell is activated, and a pharmaceutically acceptable carrier, and

2) a pharmaceutical composition comprising at least a cell selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, a mesenchymal stem cell (MSC), and any combination thereof, in combination with a Wnt/β

-catenin signalling pathway activator or an inhibitor of a Wnt/β

-catenin signalling pathway repressor, and a pharmaceutically acceptable carrier.

27. A kit selected from the group consisting of:

1) a kit comprising at least a cell selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, a mesenchymal stem cell (MSC), and any combination thereof, wherein the Wnt/β

-catenin signalling pathway of said cell is activated, and instructions for use of the kit components, and

2) a kit comprising at least a cell selected from the group consisting of a hematopoietic stem cell (HSC), a progenitor cell, a mesenchymal stem cell (MSC), and any combination thereof, in combination with a Wnt/β

-catenin signalling pathway activator or an inhibitor of a Wnt/β

-catenin signalling pathway repressor, and instructions for use of the kit components.

28. A kit according to claim 27, for use in the treatment of a retinal degeneration disease.

29. Kit for use in the treatment of a retinal degeneration disease according to claim 28, wherein said retinal degeneration disease is selected from the group consisting of retinitis pigmentosa, age-related macular degeneration, Stargardt disease, cone-rod dystrophy, congenital stationary night blindness, Leber congenital amaurosis, Best'"'"'s vitelliform macular dystrophy, anterior ischemic optic neuropathy, choroideremia, age-related macular degeneration, foveomacular dystrophy, Bietti crystalline corneoretinal dystrophy, Usher syndrome, and a retinal degenerative condition derived from a primary pathology.

30. Kit for use in the treatment of a retinal degeneration disease according to claim 28, wherein said retinal degeneration derives from cataracts, diabetes or glaucoma.