MODULATION OF NEURAL STEM CELLS AND NEURAL PROGENITOR CELLS

• US 20110189184A1
• Filed: 08/31/2010
• Published: 08/04/2011
• Est. Priority Date: 05/08/2002
• Status: Active Grant

• Current Assignee: Newron Sweden AB (Newron Pharmaceuticals Spa)
• Original Assignee: NeuroNova AB (Newron Pharmaceuticals Spa)
• Inventors: Wikström, Lilian, Lindquist, Per, Mercer, Alex, Rönnholm, Harriet
• Granted Patent: US 8,318,704 B2
• Time in Patent Office: Days
• US Class Current: 424/136.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5058 Neurological cells
• CPC Class Codes: G01N 33/5073 Stem cells

Abstract

The invention relates generally to methods of influencing central nervous system cells to produce progeny useful in the treatment of CNS disorders. More specifically, the invention includes methods of exposing a patient suffering from such a disorder to a reagent that modulates the proliferation, migration, differentiation and survival of central nervous system cells via S1P or LPA signaling. These methods are useful for reducing at least one symptom of the disorder.

Claims

1. A method of alleviating a symptom of a disorder of the nervous system in a patient comprising administering an S1P, LPA or EDG receptor agonist or a combination thereof to induce neural stem cell (NSC) proliferation in vivo to a patient suffering from the disorder of the nervous system, thereby alleviating a symptom of a disorder of the nervous system.

2. The method of claim 1 wherein the EDG receptor is selected from the group consisting of EDG1, EDG2, EDG3, EDG4, EDG5 and EDG8.

3. The method of claim 1 wherein the S1P, LPA or EDG receptor agonist or a combination thereof is administered in an amount of 0.1 ng/kg/day to 10 mg/kg/day.

4. The method of claim 1 wherein the S1P, LPA or EDG receptor agonist is administered to achieve a target tissue concentration of 0.1 nM to 10 μ

M.

5. The method of claim 4 wherein the target tissue is selected from the group consisting of the ventricular wall, the volume adjacent to the wall of the ventricular system, piriform cortex, hippocampus, alveus, striatum, substantia nigra, retina, nucleus basalis of Meynert, spinal cord, thalamus, hypothalamus piriform cortex and cortex.

6. The method of claim 1 wherein the S1P, LPA or EDG receptor agonist is administered by injection.

7. The method of claim 6 wherein the injection is given subcutaneously, intraperitoneally, intramusclularly, intracerebroventricularly, intraparenchymally, intrathecally or intracranially.

8. The method of claim 1 wherein the S1P, LPA or EDG receptor agonist is administered orally.

9. The method of claim 1 wherein the S1P, LPA or EDG receptor agonist is administered by infusion.

10. The method of claim 1 wherein the disorder of the nervous system is selected from the group consisting of neurodegenerative disorders, disorders characterized by aberrant cell proliferation, disorders characterized by aberrant cell differentiation, disorders characterized by aberrant cell proliferation and differentiation, ischemic disorders, neurological traumas, degenerative diseases of the retina, retinal injury/trauma, cognitive performance, and learning and memory disorders.

11. A method of enhancing neural stem cell proliferation in a patient suffering from a central nervous system disorder comprising administering an S1P, LPA or EDG receptor agonist or a combination thereof to said patient.

12. The method of claim 11 wherein the EDG receptor is selected from the group consisting of EDG1, EDG2, EDG3, EDG4, EDG5 and EDG8.

13. The method of claim 11 wherein the S1P, LPA or EDG receptor agonist is administered by injection.

14. The method of claim 13 wherein the injection is given subcutaneously, intraperitoneally, intramusclularly, intracerebroventricularly, intraparenchymally, intrathecally or intracranially.

15. The method of claim 11 wherein the S1P, LPA or EDG receptor agonist is administered orally.