TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS USING UMBILICAL DERIVED CELLS

• US 20110223205A1
• Filed: 02/14/2011
• Published: 09/15/2011
• Est. Priority Date: 06/27/2003
• Status: Active Grant

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: Advanced Technologies and Regenerative Medicine, LLC
• Inventors: GOSIEWSKA, Anna, Kihm, Anthony J., Harmon, Alexander M., Fang, Carrie H., Dhanaraj, Sridevi
• Granted Patent: US 8,491,883 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• 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: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2500/32 Amino acids
• CPC Class Codes: C12N 2500/34 Sugars
• CPC Class Codes: C12N 2500/44 Thiols, e.g. mercaptoethanol
• CPC Class Codes: C12N 2500/90 Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 2500/95 Protein-free medium and culture conditions
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/119 Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
• CPC Class Codes: C12N 2501/12 Hepatocyte growth factor [HGF]
• CPC Class Codes: C12N 2501/13 Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
• CPC Class Codes: C12N 2501/21 Chemokines, e.g. MIP-1, MIP-2, RANTES, MCP, PF-4
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/385 of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
• CPC Class Codes: C12N 2501/41 Hedgehog proteins; Cyclopamine (inhibitor)
• CPC Class Codes: C12N 2502/02 : embryonic cells
• CPC Class Codes: C12N 2502/03 : non-embryonic pluripotent stem cells
• CPC Class Codes: C12N 2506/02 : from embryonic 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 2509/00 : Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 2533/50 : Proteins
• CPC Class Codes: C12N 5/0605 : Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0607 : Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0622 : Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells

Abstract

This invention relates to methods of treating amyotrophic lateral sclerosis. In particular, the invention provides for methods of treating amyotrophic lateral sclerosis by administering umbilical cord tissue-derived cells, an effective amount of a substantially homogenous population of umbilical cord tissue-derived cells or a pharmaceutical composition comprising umbilical cord tissue-derived cells to a patient.

Claims

1. A method of treating amyotrophic lateral sclerosis comprising administering umbilical cord tissue-derived cells in an amount effective to treat amyotrophic lateral sclerosis to a patient, wherein the umbilical cord tissue-derived cells are isolated from human umbilical cord tissue substantially free of blood, are capable of self-renewal and expansion into culture, have the potential to differentiate into cells of other phenotypes, can undergo at least 40 doublings, and have the following characteristics:

(a) expresses each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C;

(b) does not express any of CD31, CD34, CD45, CD80, CD86, CD117, CD141, CD178, B7-H2, HLA-G, or HLA-DR, DP, DQ; and

(c) increased expression of interleukin-8;

reticulon 1; and

chemokine receptor ligand (C-X-C motif) ligand 3, relative to that of a human cell which is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

2. The method of claim 1, wherein the umbilical cord tissue-derived cells do not express hTERT or telomerase.

3. The method of claim 1, wherein the umbilical cord tissue-derived cells are induced in vitro to differentiate into a neural cell line prior to administration.

4. The method of claim 1, wherein the umbilical cord tissue-derived cells are administered with at least one other cell type of an astrocyte, oligodendrocyte, neuron, neural progenitor, neural stem cell or other multipotent or pluripotent stem cell.

5. The method of claim 1, wherein the umbilical cord tissue-derived cells are administered at a pre-determined site in the nervous system of the patient.

6. The method of claim 1, wherein the umbilical cord tissue-derived cells are administered by injection or infusion.

7. The method of claim 1, wherein umbilical cord tissue-derived cells are administered by intravenous or intrathecal injection.

8. The method of claim 1, wherein the umbilical cord tissue-derived cells are administered encapsulated within an implantable device.

9. The method of claim 1, wherein the umbilical cord tissue-derived cells are administered by implantation of a matrix or scaffold containing the cells.

10. The method of claim 1, wherein the umbilical cord tissue-derived cells exert a trophic effect on the nervous system of the patient.

11. The method of claim 1, wherein the umbilical cord tissue-derived cells are genetically engineered to produce a gene product that promotes treatment of the neurodegenerative condition.

12. A method of treating amyotrophic lateral sclerosis comprising administering an effective amount of a substantially homogeneous population of umbilical cord tissue-derived cells to a patient, wherein the population of umbilical cord tissue-derived cells is isolated from human umbilical cord tissue substantially free of blood, is capable of self-renewal and expansion into culture, has the potential to differentiate into cells of other phenotypes, can undergo at least 40 doublings, and has the following characteristics:

(a) expresses each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C;

(b) does not express any of CD31, CD34, CD45, CD80, CD86, CD 117, CD141, CD178, B7-H2, HLA-G, or HLA-DR, DP, DQ; and

(c) increased expression of interleukin-8;

reticulon 1; and

chemokine receptor ligand (C-X-C motif) ligand 3, relative to that of a human cell which is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

13. The method of claim 12, wherein the umbilical cord tissue-derived cells do not express hTERT or telomerase.

14. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells is induced in vitro to differentiate into a neural cell line prior to administration.

15. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells is administered with at least one other cell type of an astrocyte, oligodendrocyte, neuron, neural progenitor, neural stem cell or other multipotent or pluripotent stem cell.

16. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells is administered at a pre-determined site in the nervous system of the patient.

17. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells is administered by injection or infusion.

18. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells is administered by intravenous or intrathecal injection.

19. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells is encapsulated within an implantable device.

20. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells is administered by implantation of a matrix or scaffold containing the cells.

21. The method of claim 12, wherein the substantially homogeneous population of umbilical cord tissue-derived cells exerts a trophic effect on the nervous system of the patient.

22. A method of treating amyotrophic lateral sclerosis comprising administering a pharmaceutical composition comprising umbilical cord tissue-derived cells in an amount effective to treat amyotrophic lateral sclerosis to a patient, wherein the umbilical cord tissue-derived cells are isolated from human umbilical cord tissue substantially free of blood, are capable of self-renewal and expansion into culture, have the potential to differentiate into cells of other phenotypes, can undergo at least 40 doublings, and have the following characteristics:

(a) expresses each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C;

(b) does not express any of CD31, CD34, CD45, CD80, CD86, CD 117, CD141, CD178, B7-H2, HLA-G, or HLA-DR, DP, DQ; and

(c) increased expression of interleukin-8;

reticulon 1; and

chemokine receptor ligand (C-X-C motif) ligand 3, relative to that of a human cell which is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

23. The method of claim 22, wherein the umbilical cord tissue-derived cells do not express hTERT or telomerase.

24. The method of claim 22, wherein the umbilical cord tissue-derived cells are induced in vitro to differentiate into a neural cell line prior to administration.

25. The method of claim 22, wherein the pharmaceutical composition is administered with at least one other cell type of an astrocyte, oligodendrocyte, neuron, neural progenitor, neural stem cell or other multipotent or pluripotent stem cell.

26. The method of claim 22, wherein the pharmaceutical composition is administered at a pre-determined site in the nervous system of the patient.

27. The method of claim 22, wherein the pharmaceutical composition is administered by injection or infusion.

28. The method of claim 22, wherein the pharmaceutical composition is administered by intravenous or intrathecal injection.

29. The method of claim 22, wherein the pharmaceutical composition is encapsulated within an implantable device.

30. The method of claim 22, wherein the pharmaceutical composition is administered by implantation of a matrix or scaffold containing the cells.