Use of human neural stem cells secreting GDNF for treatment of parkinson's and other neurodegenerative diseases

• US 20030228295A1
• Filed: 04/25/2003
• Published: 12/11/2003
• Est. Priority Date: 04/25/2002
• Status: Abandoned Application

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Svendsen, Clive N.
• Application Number:
  US10/423,710
• Publication Number:
  US 20030228295A1
• Time in Patent Office: Days
• US Class Current: 424/93.21
• CPC Class Codes: A01K 67/0339 Genetically modified insects, e.g. Drosophila melanogaster, medfly
• 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: A61K 48/0058 Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2740/15043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus

Abstract

A method of treating brain disorders involving loss of cells that respond to GDNF is disclosed. In one embodiment, the invention comprises the steps of (a) transducing human neural stem cells with glial-derived neurotrophic factor (GDNF), wherein the GDNF gene is under control of an inducible promoter system, and (b) transplanting the transduced cells into the brain of a patient.

Claims

1. A method of treating brain disorders involving loss of cells that respond to GDNF comprising the steps of

(a) transducing human neural stem cells with glial-derived neurotrophic factor (GDNF), wherein the GDNF gene is under control of an inducible promoter system, and

(b) transplanting the transduced cells into the brain of a patient, wherein GDNF is expressed.

2. The method of claim 1 wherein the patient'"'"'s GDNF-responsive neuron system is up-regulated.

3. The method of claim 1 wherein the disorder is Parkinson'"'"'s Disease.

4. The method of claim 3 wherein the GDNF-responsive neuron system is the dopaminergic system.

5. The method of claim 1 wherein the disorder is selected from the group consisting of Parkinson'"'"'s Disease, amyotrophic lateral sclerosis, Huntington'"'"'s Disease, and stroke.

6. The method of claim 1 wherein the inducible promoter system is the mouse phosphoglycerate kinase 1/tTA1 system.

7. The method of claim 1 wherein the human neural cells are grown as neurospheres.

8. The method of claim 1 wherein the cells are derived from post-mortem fetal brain tissue.

9. The method of claim 1 wherein the transplanted cells migrate and integrate into the patient'"'"'s brain.

10. The method of claim 1 wherein the cells are transplanted into the brain putamen.

11. The method of claim 10 wherein the cells are transplanted into the caudal half of the brain putamen.

12. The method of claim 1 wherein the transduced cells comprise an additional heterologous growth factor.

13. A viral vector useful for the method of claim 1, wherein the viral vector comprises an inducible promoter and a sequence encoding GDNF.

14. The vector fo claim 13, wherein the vector is a lentivirus.

15. The vector of claim 14 wherein the vector comprises the mouse phosphoglycerate kinase 1 promoter operably connected to tTA1 and the post-translational cis-acting regulatory element of the woodchuck hepatitis virus.

16. The vector of claim 15 wherein administration of doxycycline would activate GDNF expression.

17. The vector of claim 15 wherein administration of doxycycline would inactivate GDNF expression.