hUTC as therapy for Alzheimer's disease

• US 9,943,552 B2
• Filed: 04/03/2014
• Issued: 04/17/2018
• Est. Priority Date: 03/26/2009
• Status: Active Grant

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Inventors: Kihm, Anthony J., Gosiewska, Anna
• Primary Examiner(s): Hill, Kevin K
• Application Number:
  US14/244,426
• Publication Number:
  US 20140234277A1
• Time in Patent Office: 1,475 Days
• 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 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C12N 15/63 Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• CPC Class Codes: C12N 2509/00 Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/10 Cells modified by introduction of foreign genetic material

Abstract

Methods for treating Alzheimer'"'"'s disease, or the symptoms of Alzheimer'"'"'s disease, are provided. Some embodiments are to methods for treatment comprising administering cells obtained from human umbilical cord tissue, or administering pharmaceutical compositions comprising such cells or prepared from such cells, such as cell derivatives. Some embodiments are to methods for treatment comprising hUTC. Pharmaceutical compositions for use in the inventive methods, as well as kits for practicing the methods are also provided.

Claims

1. A method of reducing the accumulation of amyloid plaque proteins in a subject diagnosed with Alzheimer'"'"'s disease, or having symptoms of Alzheimer'"'"'s disease, comprising locally administering to a neuritic plaque site in the brain of the subject a composition comprising an undifferentiated population of isolated human umbilical cord-derived cells,

wherein the isolated human umbilical cord-derived cells are obtained from human umbilical cord tissue substantially free of blood;

wherein the isolated cells self-renew and expand in culture and do not express CD117; and

wherein the locally administered undifferentiated population of isolated human umbilical cord-derived cells reduce the accumulation of amyloid plaque proteins in the subject.

2. The method of claim 1, wherein the isolated human umbilical cord-derived cells are administered to cerebral spinal fluid.

3. The method of claim 1, said composition further comprising pharmaceutically acceptable carriers and/or diluents selected from the group consisting of:

saline, aqueous buffer solutions, solvents, artificial cerebral spinal fluid, dispersion media composition and a mix thereof.

4. The method of claim 1, wherein the human umbilical cord-derived cells that do not express CD117 further have one or more of the following characteristics:

expression of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C;

lack of expression of CD31, CD34, CD45, CD141, or HLA-DR,DP,DQ; and

increased expression of a gene encoding interleukin 8 and reticulon 1, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

5. The method of claim 1, wherein the human umbilical cord-derived cells further have each of the following characteristics:

expression of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C;

lack of expression of CD31, CD34, CD45, CD117, CD141, or HLA-DR,DP,DQ; and

increased expression of a gene encoding interleukin 8 and reticulon 1, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

8. The method of claim 1, wherein the cells are not genetically modified to produce therapeutically useful gene products, to produce agents to facilitate or support neural tissue survival, differentiation, phagocytic activity, or to produce factors to recruit progenitor cells to the area of neuritic plaques.

6. A method of treating a subject diagnosed with Alzheimer'"'"'s disease comprising locally administering to a neuritic plaque site in the brain of the subject a composition comprising an undifferentiated population of isolated human umbilical cord-derived cells,

wherein the locally administered undifferentiated population of isolated human umbilical cord-derived cells facilitates plaque removal by phagocytic mechanisms,

wherein the isolated human umbilical cord-derived cells are obtained from human umbilical cord tissue substantially free of blood, and

wherein the isolated cells self-renew and expand in culture and have following characteristics:

expression of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C;

lack of expression of CD31, CD34, CD45, CD117, CD141, or HLA-DR,DP,DQ; and

increased expression of a gene encoding interleukin 8 and reticulon 1, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

9. The method of claim 6, wherein the cells are not genetically modified to produce therapeutically useful gene products, to produce agents to facilitate or support neural tissue survival, differentiation, phagocytic activity, or to produce factors to recruit progenitor cells to the area of neuritic plaques.

7. A method of treating a subject having symptoms of Alzheimer'"'"'s disease comprising locally administering to a neuritic plaque site in the brain of the subject a composition comprising an undifferentiated population of isolated human umbilical cord-derived cells,

wherein the locally administered undifferentiated population of isolated human umbilical cord-derived cells facilitates plaque removal by phagocytic mechanisms,

wherein the isolated human umbilical cord-derived cells are obtained from human umbilical cord tissue substantially free of blood, and

wherein the isolated cells self-renew and expand in culture and have following characteristics:

expression of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C;

lack of expression of CD31, CD34, CD45, CD117, CD141, or HLA-DR,DP,DQ; and

increased expression of a gene encoding interleukin 8 and reticulon 1, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

10. The method of claim 7, wherein the cells are not genetically modified to produce therapeutically useful gene products, to produce agents to facilitate or support neural tissue survival, differentiation, phagocytic activity, or to produce factors to recruit progenitor cells to the area of neuritic plaques.