Use of marrow-derived glial progenitor cells as gene delivery vehicles into the central nervous system

• US 7,022,321 B2
• Filed: 04/11/2002
• Issued: 04/04/2006
• Est. Priority Date: 04/10/1997
• Status: Expired due to Fees

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Inventors: Mouradian, Mary Maral, Mezey, Eva, Eglitis, Martin A.
• Primary Examiner(s): FALK, ANNE MARIE
• Application Number:
  US10/122,703
• Publication Number:
  US 20030003087A1
• Time in Patent Office: 1,454 Days
• Field of Search: 424/93.1, 424/93.2, 424/93.21
• US Class Current: 424/93.21
• 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 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2501/125 Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2510/02 Cells for production
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

The present disclosure relates to a method for introducing a hematopoietic cell into the brain of a mammal, by administering bone marrow-derived progenitor cells into the body of the mammal by intravenous injection. The bone marrow-derived cell is preferably a cell that differentiates into a glial cell.

The disclosure also relates to a method for delivery of therapeutic protein molecules into the brain of a mammal, by administering to a mammal an effective amount of bone marrow-derived progenitor cells which contain a gene having a nucleic acid sequence that encodes a functional therapeutic protein.

Isolated recombinant cells and a pharmaceutical composition are also provided.

Claims

1. A method of treating Parkinson'"'"'s disease, comprising:

transfecting harvested bone marrow cells with a retroviral vector comprising a gene for glial cell line-derived neurotrophic factor (GDNF);

administering the transfected cells intravenously to a subject having Parkinson'"'"'s disease; and

allowing the transfected cells to migrate to the brain of the subject and express the GDNF gene, thereby treating the Parkinson'"'"'s disease.

2. The method of claim 1, wherein the transfected cells differentiate into astroglia and microglia in the brain of the subject.

3. The method of claim 1, wherein the transfected cells migrate to the cortex, hippocampus, thalamus, brainstem or cerebellum of the brain.

4. The method of claim 1, further comprising culturing the harvested bone marrow in vitro in a cell culture medium comprising IL-3, IL-6, and stem cell factor prior to transfection with the GDNF gene.

5. The method of claim 4, wherein the harvested bone marrow is cultured in vitro for 48 hours.

6. The method of claim 1, wherein the subject has been sub-lethally irradiated prior to administration of the transfected cells.

7. The method of claim 1, wherein the retroviral vector is a Moloney murine leukemia virus vector.

8. A method of treating Parkinson'"'"'s disease, comprising:

culturing harvested bone marrow cells in a cell culture medium comprising IL-3, IL-6, and stem cell factor;

transfecting the harvested bone marrow cells with a Moloney murine leukemia virus vector comprising a gene for glial cell line-derived neurotrophic factor (GDNF);

administering the transfected cells intravenously to a subject having Parkinson'"'"'s disease; and

allowing the transfected cells to migrate to the brain of the subject and express the GDNF gene, thereby treating the Parkinson'"'"'s disease.