Modulation of neural stem cells and neural progenitor cells

• US 7,811,822 B2
• Filed: 07/19/2007
• Issued: 10/12/2010
• Est. Priority Date: 05/08/2002
• Status: Expired due to Fees

• Current Assignee: Newron Sweden AB (Newron Pharmaceuticals Spa)
• Original Assignee: NeuroNova AB (Newron Pharmaceuticals Spa)
• Inventors: Ronnholm, Harriet, Lindquist, Per, Mercer, Alex, Wikstrom, Lilian
• Primary Examiner(s): Nickol; Gary B.
• Assistant Examiner(s): Gamett; Daniel C
• Application Number:
  US11/880,213
• Publication Number:
  US 20080213276A1
• Time in Patent Office: 1,181 Days
• Field of Search: None
• US Class Current: 435/377
• 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 modulating the activity of an S1P, LPA, EDG receptor or a combination thereof, on an adult neural stem cell (NSC) comprising the step of exposing the cell expressing the receptor to a modulator agent selected from the group consisting of S1P, LPA or EDG receptor agonist, wherein the exposure induces increased NSC proliferation compared to untreated cells, and wherein the NSC is derived from adult brain, neural cell culture or a neurosphere.

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. A method for stimulating mammalian adult NSC proliferation comprising the step of contacting a cell population comprising mammalian adult NSC to an agent selected from the group consisting of an S1P, LPA or EDG receptor agonist to form a treated NSC, wherein the treated NSC cell shows increased proliferation compared to untreated cells, and wherein the NSC is derived from lateral ventricle wall of a mammalian brain.

4. The method of claim 3 wherein the EDG receptor is selected from the group consisting of EDG1, EDG2, EDG3, EDG4, EDG5 and EDG8.

5. A method for stimulating primary adult mammalian NSC to proliferate to form neurospheres comprising contacting the cell with an agent selected from the group consisting of an S1P, LPA or EDG receptor agonist to produce a proliferating NSC.

6. The method of claim 5 wherein the EDG receptor is selected from the group consisting of EDG1, EDG2, EDG3, EDG4, EDG5 and EDG8.

7. A method of enhancing neural stem cell proliferation in a patient having a central nervous system disorder comprising the step of infusing an S1P, LPA or EDG receptor agonist thereof into the patient, wherein neural stem cells show increased proliferation compared to untreated cells.

8. The method of claim 7 wherein the EDG receptor is selected from the group consisting of EDG1, EDG2, EDG3, EDG4, EDG5 and EDG8.

9. The method of claim 7 wherein the infusion is selected from the group consisting of intraventricular, intravenous, sublingual, subcutaneous and intraarterial infusion.