Modulation of neural stem cells and neural progenitor cells
First Claim
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 modulate NSC activity in vivo to a patient suffering from the disorder of the nervous system.
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Accused Products
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.
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Citations
66 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 modulate NSC activity in vivo to a patient suffering from the disorder of the nervous system.
- 12. A method of modulating the activity of an S1P, LPA, EDG receptor or a combination thereof, on a NSC comprising the step of exposing the cell expressing the receptor to a modulator agent, wherein the exposure induces an NSC to proliferate, differentiate, migrate or survive.
- 21. A method for stimulating mammalian adult NSC proliferation or neurogenesis comprising the step of contacting a cell population comprising mammalian adult NSC to a 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 improved proliferation or neurogenesis compared to untreated cells.
- 26. 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.
- 28. A method for inducing the in situ proliferation, migration or survival of an NSC located in the neural tissue of a mammal, the method comprising administering a therapeutically effective amount of an S1P, LPA or EDG receptor agonist to the neural tissue to induce the proliferation, migration or survival of the cell.
- 30. A method of enhancing neurogenesis in a patient suffering from a central nervous system disorder comprising the step of infusing an S1P, LPA or EDG receptor agonist thereof into the patient.
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33. A method of alleviating a symptom of a central nervous system disorder in a patient comprising the step of infusing an S1P, LPA or EDG receptor agonist into the patient.
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34. A method for producing a cell population enriched for human NSC, comprising:
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(a) contacting a cell population containing NSC with a reagent that recognizes a determinant on an S1P, LPA or EDG receptor; and
(b) selecting for cells in which there is contact between the reagent and the determinant on the surface of the cells of step (a) to produce a population highly enriched for central nervous system stem cells. - View Dependent Claims (35, 36, 37, 38, 39, 40, 41, 42)
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43. A method of reducing a symptom of a central nervous system disorder in a patient comprising the step of administering into the spinal cord of the subject a composition comprising
(a) a population of isolated NSCs obtained from fetal or adult tissue; - and
(b) an S1P, LPA or EDG receptor agonist or a combination thereof;
whereby the symptom is reduced. - View Dependent Claims (44)
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45. A method of reducing a symptom of a central nervous disorder in a patient comprising the steps of:
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(a) introducing a viral vector into the target cell, wherein the viral vector has at least one insertion site containing a nucleic acid which encodes an S1P, LPA or EDG receptor agonist, the nucleic acid gene operably linked to a promoter capable of expression in the host; and
(b) expressing the nucleic acid to produce a protein in a target cell to reduce the symptom. - View Dependent Claims (46)
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47. A method for alleviating a symptom of a disease or disorder of the nervous system in a patient comprising the steps of:
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(a) providing a population of NSC;
(b) suspending the NSC in a solution comprising an S1P, LPA or EDG receptor agonist or a combination thereof to generate a cell suspension; and
(c) delivering the cell suspension to an injection site in the nervous system of the patient to alleviate the symptom. - View Dependent Claims (48, 49, 50)
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51. A method for transplanting a population of cells enriched for human NSC, comprising:
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(a) contacting a population containing NSC with a reagent that recognizes a determinant on an S1P, LPA or EDG receptor;
(b) selecting for cells in which there is contact between the reagent and the determinant on the surface of the cells of step (a), to produce a population highly enriched for central nervous system stem cells; and
(c) implanting the selected cells of step (b) into a non-human mammal. - View Dependent Claims (52)
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- 53. A method of modulating an S1P, LPA or EDG receptor agonist on the surface of an NSC comprising the step of contacting the cell expressing the receptor to exogenous reagent, antibody, or affibody, wherein the exposure induces the NSC to proliferate, migrate or survive.
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56. A method of determining an isolated candidate S1P, LPA or EDG receptor modulator compound for its ability to modulate NSC activity comprising the steps of:
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(a) administering the isolated candidate compound to a non-human mammal; and
(b) determining if the candidate compound has an effect on modulating the NSC activity in the non-human mammal. - View Dependent Claims (57, 58, 59, 60, 61, 62)
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- 63. A method for synergistically stimulating mammalian adult NSC proliferation or neurogenesis comprising the step of contacting a cell population comprising mammalian adult neural stem cells to a growth factor and an agent selected from the group consisting of an S1P, LPA and EDG receptor agonist.
Specification