Methods of treating multiple sclerosis using STRO-1+ and TNAP+ multipotential cells

• US 10,206,951 B2
• Filed: 06/04/2012
• Issued: 02/19/2019
• Est. Priority Date: 06/03/2011
• Status: Active Grant

• Current Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Original Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Inventors: Bernard, Claude
• Primary Examiner(s): Wang, Chang-Yu
• Application Number:
  US14/123,758
• Publication Number:
  US 20140322276A1
• Time in Patent Office: 2,451 Days
• 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 a subject with multiple sclerosis, the method comprising administering to the subject a population of cells enriched for STRO-1⁺ TNAP⁺ multipotential cells in an amount effective to treat the subject.

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

3. The method of claim 1, wherein the multiple sclerosis is a chronic progressive form of multiple sclerosis or a relapsing-remitting form of multiple sclerosis.

4. The method of claim 1, wherein the population enriched for STRO-1⁺ TNAP⁺ multipotential cells is administered systemically.

5. The method of claim 1, comprising:

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

(ii) administering between 2×

10⁶ and 8×

10⁶ STRO-1⁺ TNAP⁺ multipotential cells per kg;

(iii) administering between 3×

10⁶ and 6×

10⁶ STRO-1⁺ TNAP⁺ multipotential cells per kg;

or

(iv) administering a low dose of STRO-1⁺ TNAP⁺ multipotential cells,

wherein the low dose of STRO-1⁺ TNAP⁺ cells comprises between 0.1×

10⁶ and 3×

10⁶ STRO-1⁺ cells per kg or comprises about 3×

10⁶ STRO-1⁺ TNAP⁺ cells.

6. The method of claim 1, wherein the population enriched for STRO-1⁺ TNAP⁺ multipotential cells is administered once weekly or is administered once every four weeks.

7. The method of claim 1, wherein the population enriched for STRO-1⁺ TNAP⁺ multipotential cells is autogeneic or allogeneic.

8. The method of claim 1, wherein the population enriched for STRO-1⁺ TNAP⁺ multipotential cells has been culture expanded prior to administration.

9. A method for treating a subject with multiple sclerosis, the method comprising administering to the subject a population of cells enriched for STRO-1⁺ TNAP⁺ multipotential cells such that at least 5% of the cells are STRO-1⁺ TNAP⁺ multipotential cells so as to treat the subject.