METHODS OF TREATING OR PREVENTING NEUROLOGICAL DISEASES

• US 20140322276A1
• Filed: 06/04/2012
• Published: 10/30/2014
• Est. Priority Date: 06/03/2011
• Status: Active Grant

• Current Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Original Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Inventors: Bernard, Claude
• Granted Patent: US 10,206,951 B2
• Time in Patent Office: Days
• US Class Current: 424/278.1
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2506/00 Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
• CPC Class Codes: C12N 2506/025 from extra-embryonic cells, e.g. trophoblast, placenta
• CPC Class Codes: C12N 2506/03 from non-embryonic pluripotent stem cells
• CPC Class Codes: C12N 2506/08 from cells of the nervous system
• CPC Class Codes: C12N 2506/11 from blood or immune system cells
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: G01N 2333/435 from animals; from humans
• CPC Class Codes: G01N 2333/70503 Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
• CPC Class Codes: G01N 2800/24 : Immunology or allergic disorders SLE G01N2800/104
• CPC Class Codes: G01N 2800/28 : Neurological disorders

Abstract

The present disclosure provides a method for treating an inflammatory neurological disease comprising administering a population of cells enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom.

Claims

1. A method for treating or preventing an inflammatory neurological disease, the method comprising administering to the subject a population of cells enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom.

2. The method of claim 1, wherein the inflammatory neurological disease is associated with or caused by a T cell response to an inflammatory stimulus.

3. The method of claim 1 comprising administering a population of cells enriched for STRO-1^bright cells and/or progeny thereof and/or soluble factors derived therefrom.

4. The method of claim 1, wherein the inflammatory neurological disease is selected from the group consisting of multiple sclerosis, systemic lupus erythematosus, Guillain-Barre syndrome, Lambert-Eaton myasthenic syndrome, myasthenia gravis, transverse myelitis, leukodystrophy and progressive multifocal leukoencephalopathy.

5. The method of claim 1, wherein the disease is systemic lupus erythematosus or multiple sclerosis.

7. The method of claim 5, wherein the disease is a chronic progressive form of multiple sclerosis or a relapsing-remitting form of multiple sclerosis.

8. The method of claim 1, wherein the population enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom are administered systemically.

10. The method of claim 1, comprising:

(i) administering an amount of the population enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom effective to increase the number of regulatory T (Treg) cells in the subject and/or at the site of pathogenesis of the disease;

(ii) The method of claim 1, comprising administering between 2×

10⁶ to 8×

10⁶ STRO-1⁺ cells and/or progeny thereof per kg;

(iii) The method of claim 1, comprising administering between 3×

10⁶ to 6×

10⁶ STRO-1⁺ cells and/or progeny thereof per kg;

or

(iv) The method of claim 1 comprising administering a low dose of STRO-1⁺ cells and/or progeny thereof.

14. The method of claim 10, wherein the low dose of STRO-1⁺ cells and/or progeny thereof comprises between 0.1×

10⁶ and 3×

10⁶ STRO-1⁺ cells and/or progeny thereof per kg or comprises about 3×

10⁶ STRO-1⁺ cells and/or progeny thereof per kg.

16. The method of claim 1, wherein the population enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom are administered once weekly or less often or are administered once every four weeks or less often.

18. The method of claim 1, wherein the population enriched for STRO-1⁺ cells and/or progeny thereof are genetically-engineered to express a molecule to block stimulation of T cells and/or the soluble factors are from such genetically-modified cells or wherein the population enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors therefrom are administered with a compound to block stimulation of T cells.

20. The method of claim 1, wherein the population enriched for STRO-1⁺ cells and/or progeny cells are autogeneic or allogeneic and/or the soluble factors are derived from autogeneic or allogeneic cells.

21. The method of claim 1, wherein the population enriched for STRO-1⁺ cells and/or progeny cells have been culture expanded prior to administration and/or prior to obtaining the soluble factors.

32. The method of claim 1, wherein the population of cells enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom is administered with a compound that treats or prevents an inflammatory neurological disease.

6. (canceled)

9. (canceled)

11-13. -13. (canceled)

15. (canceled)

17. (canceled)

19. (canceled)

22. A method for preventing an immune response in response to an antigen, the method comprising administering to the subject a population of cells enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom.

23. The method of claim 22, wherein the immune response is a T cell-mediated immune response.

25. The method of claim 22, wherein the T cell-mediated immune response is suppressed in response to a specific antigen and a T cell-mediated immune response in response to another antigen is not suppressed.

26. The method of claim 22, wherein the subject has previously raised an immune response to the antigen and the population, progeny and/or soluble factors suppress a further immune response to the antigen.

27. The method of claim 26, comprising administering the population, progeny and/or soluble factors after the subject raises an immune response to the antigen to thereby prevent a further immune response to the antigen.

28. The method of claim 22, wherein the immune response is suppressed for at least about 24 days following administration of the population of cells enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom.

30. The method of claim 22, wherein the antigen or the specific antigen is one against which an inflammatory response is raised.

31. The method of claim 30, wherein the inflammatory response is causative of an inflammatory neurological disease.

24. (canceled)

29. A method for inducing tolerance to an antigen in a subject, the method comprising administering to the subject a population of cells enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom.

33-35. -35. (canceled)