Neuronal progenitor cells and uses thereof

• US 20010024827A1
• Filed: 05/08/2001
• Published: 09/27/2001
• Est. Priority Date: 07/06/1995
• Status: Abandoned Application

• Current Assignee: Emory University
• Original Assignee: Emory University
• Inventors: Luskin, Marla B.
• Application Number:
  US09/850,769
• Publication Number:
  US 20010024827A1
• Time in Patent Office: Days
• US Class Current: 435/375
• 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 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: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 5/0623 Stem cells
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025

Abstract

The present invention provides an isolated cellular composition comprising greater than about 90% mammalian, non tumor-derived, neuronal progenitor cells which express a neuron-specific marker and which can give rise to progeny which can differentiate into neuronal cells. Also provided are methods of treating neuronal disorders utilizing this cellular composition.

Claims

1. An isolated cellular composition comprising greater than about 90% mammalian, non tumor-derived, neuronal progenitor cells which express a neuron-specific marker and which can give rise to progeny which can differentiate into neuronal cells.

2. The composition of

claim 1

, wherein greater than about 95% of the mammalian, non tumor-derived, neuronal progenitor cells express a neuronal marker and can give rise to progeny which can differentiate into neuronal cells.

3. The composition of

claim 1

, wherein the isolated neuronal progenitor cells can, without being first immortalized, divide for at least two generations.

4. The composition of

claim 1

, wherein the neuronal progenitor cells are rat cells.

5. The composition of

claim 1

, wherein the neuronal progenitor cells are human cells.

6. The composition of

claim 1

, wherein at least a portion of the population of neuronal progenitor cells, or their progeny, is transfected with an exogenous nucleic acid.

7. The composition of

claim 6

, wherein the exogenous nucleic acid functionally encodes a biologically active molecule.

8. The composition of

claim 7

, wherein the exogenous nucleic acid functionally encodes a biologically active molecule that stimulates cell division or differentiation.

9. The composition of

claim 7

, wherein the exogenous nucleic acid functionally encodes a biologically active molecule that functions in the synthesis of a neurotransmitter.

10. A method of delivering a biologically active molecule produced by the neuronal progenitor cells of the cellular composition of

claim 1

, or their progeny, or mixtures thereof, to a region of a mammalian brain comprising transplanting the cellular composition of

claim 1

into the region of the brain, thereby delivering a biologically active molecule produced by the cells or their progeny to the region.

11. A method of delivering a biologically active molecule produced by the neuronal progenitor cells of the cellular composition of

claim 7

, or their progeny, or mixtures thereof, to a region of a mammalian brain comprising transplanting the cellular composition of

claim 7

into the region of the brain, thereby delivering the biologically active molecule produced by the cells or their progeny to the region.

12. A method of treating a neuronal disorder characterized by a reduction of catecholamines in the brain of a mammal, comprising transplanting into the brain the cellular composition of

claim 1

, or their progeny, or mixtures thereof, thereby providing a source of catecholamines to the brain and treating the disorder.

13. The method of

claim 12

, wherein the neuronal disorder is Parkinson'"'"'s disease.

14. A method of treating Alzheimer'"'"'s disease in a subject comprising transplanting into the brain of the subject the cellular composition of

claim 8

, or their progeny, or mixtures thereof, thereby treating Alzheimer'"'"'s disease.

15. A method of treating Alzheimer'"'"'s disease in a subject comprising transplanting into the brain of the subject the cellular composition of

claim 9

, or their progeny, or mixtures thereof, thereby treating Alzheimer'"'"'s disease.

16. A method of treating a neuronal disorder characterized by a reduction of γ

-aminobutyric acid in the brain in a mammal, comprising transplanting into the brain the cellular composition of

claim 1

, or their progeny, or mixtures thereof, thereby providing a source of γ

-aminobutyric acid to the brain and treating the disorder.

17. The method of

claim 16

, wherein the neuronal disorder is Huntington'"'"'s Disease.

18. A method of screening for a marker of neuronal cells comprising obtaining the neuronal progenitor cells of

claim 1

, and detecting the presence of a marker in the neuronal progenitor cells that is not present in non-neuronal cells, the marker present in the neuronal progenitor cells that is not present in the non-neuronal cells being a marker of neuronal cells.

19. A method of detecting a neuronally expressed gene comprising obtaining a cDNA library from the neuronal progenitor cells of

claim 1

, obtaining a cDNA library from a non-neuronal cell, determining the presence at higher levels of a cDNA in the library from the neuronal progenitor cells than in the non-neuronal cell, the presence at higher levels of a cDNA in the library from the neuronal progenitor cells indicating a neuronally expressed gene.

20. A method of obtaining an isolated cellular composition comprising greater than about 90% mammalian, non tumor-derived, neuronal progenitor cells which express a neuronal marker and which can give rise to progeny which can differentiate into neuronal cells, comprising isolating cells from the portion of a mammalian brain that is the equivalent of the anterior portion of the subventricular zone at the dorsolateral portion of the anterior-most extent of the region surrounding the ventricle of a neonatal rat brain and culturing the isolated cells in the absence of mitotic inhibitors.

21. An isolated cellular composition comprising greater than about 50% mammalian, non tumor-derived, neuronal progenitor cells which express a neuron-specific marker and which give rise to progeny which can differentiate into neuronal cells.