Claims
- 1. A method of inhibiting or reducing symptoms of Alzheimer's disease in a patient, comprising the step of administering to the Alzheimer's disease patient a therapeutically effective composition, comprising a pharmaceutically acceptable amount of a GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, that is sufficient to block or inhibit activity of GSK-3 or GSK-3α in the patient.
- 2. The method of claim 1, wherein the patient is a mammal.
- 3. The method of claim 1, wherein the mammal is a transgenic mammal.
- 4. The method of claim 2, wherein the mammal is human.
- 5. The method of claim 1, wherein the GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, comprises lithium or a salt thereof.
- 6. The method of claim 1, wherein the patient's requirement for other medication to treat Alzheimer's disease and the patient's symptoms related thereto is reduced.
- 7. The method of claim 1, wherein blocking or inhibiting the GSK-3 activity or the GSK-3α-specific activity, or a combination thereof, in the patient results in reducing formation of Aβ amyloid plaques.
- 8. The method of claim 7, wherein blocking, inhibiting or reducing GSK-3 activity in the patient results in blocking, inhibiting or reducing production of Aβ40 and Aβ42 peptides, whereas blocking, inhibiting or reducing GSK-3α activity disrupts γ-secretase cleavage of APP, without inhibiting Notch processing.
- 9. A method for treating a condition, disease or disorder mediated by GSK-3α activity, comprising the step of administering a selective inhibitor of GSK-3α.
- 10. The method of claim 9, wherein the selective inhibiting of GSK-3α comprises administering a therapeutically effective composition comprising a pharmaceutically acceptable amount of GSK-3α inhibitor that is sufficient to block, inhibit or reduce GSK-3α activity.
- 11. The method of claim 10, wherein the method comprises treating a condition, disease or disorder mediated by GSK-3 activity or GSK-3α activity in a patient, and the treatment comprises administering to the patient a therapeutically effective composition, comprising a pharmaceutically acceptable amount of GSK-3 inhibitor or GSK-3α-specific inhibitor that is sufficient to block or inhibit activity of GSK-3 or GSK-3α, respectively.
- 12. The method of claim 11, wherein the patient has Alzheimer's disease.
- 13. The method of claim 11, wherein the patient is a mammal.
- 14. The method of claim 13, wherein the mammal is a transgenic mammal.
- 15. The method of claim 13, wherein the mammal is human.
- 16. The method of claim 11, wherein the GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, comprises lithium or a salt thereof.
- 17. The method of claim 11, wherein the method comprises treating a condition, disease or disorder in vitro that is mediated by GSK-3 or GSK-3α activity, respectively, in brain cells or tissues and the treatment comprises exposing the brain cells or tissue to a therapeutically effective composition, comprising a pharmaceutically acceptable amount of GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, that is sufficient to block or inhibit activity of GSK-3 or GSK-3α, respectively.
- 18. The method of claim 17, wherein the GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, comprises lithium or a salt thereof.
- 19. The method of claim 17, wherein the brain cells or tissues are from an Alzheimer's disease patient.
- 20. A method of stabilizing a patient susceptible to a condition, disease or disorder mediated by GSK-3α activity, comprising the step of administering to the patient a therapeutically effective composition, comprising a pharmaceutically acceptable amount of GSK-3α-specific inhibitor that is sufficient to block or inhibit activity of GSK-3α.
- 21. The method of claim 20, wherein the patient is susceptible to Alzheimer's disease.
- 22. The method of claim 20, wherein the patient is a mammal.
- 23. The method of claim 22, wherein the mammal is human.
- 24. A method of preventing a condition, disease or disorder mediated by GSK-3α activity, comprising the step of administering to the patient a therapeutically effective composition, comprising a pharmaceutically acceptable amount of GSK-3α-specific inhibitor that is sufficient to block, inhibit or reduce activity of GSK-3α.
- 25. The method of claim 24, wherein the condition, disease or disorder mediated by GSK-3α activity is Alzheimer's disease.
- 26. The method of claim 24, wherein the condition, disease or disorder mediated by GSK-3α occurs in brain cells or tissues and the pharmaceutically acceptable amount of GSK-3α-specific inhibitor that is sufficient to block, reduce or inhibit activity of GSK-3α is administered to the brain cells or tissues.
- 27. The method of claim 24, wherein the condition, disease or disorder mediated by GSK-3α occurs in a patient, and the pharmaceutically acceptable amount of GSK-3α-specific inhibitor that is sufficient to block, reduce or inhibit activity of GSK-3α is administered to the patient.
- 28. The method of claim 27, wherein the patient is a mammal.
- 29. The method of claim 28, wherein the mammal is human.
- 30. A method of delaying onset of symptoms of Alzheimer's disease in a patient, comprising the step of administering to the patient susceptible to the onset of Alzheimer's disease a therapeutically effective composition, comprising a pharmaceutically acceptable amount of GSK-3α-specific inhibitor that is sufficient to block or inhibit activity of GSK-3α in the patient leading to the onset of the disease.
- 31. The method of claim 30, wherein the patient is a mammal.
- 32. The method of claim 31, wherein the mammal is human.
- 33. A kit for selectively inhibiting GSK-3 or GSK-3α, respectively, comprising a therapeutically effective composition, comprising a pharmaceutically acceptable amount of GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, that is sufficient to block or inhibit activity of GSK-3 or GSK-3α, respectively, and an instructional material regarding the use thereof to treat a condition, disease or disorder mediated by GSK-3 or GSK-3α activity in a patient, or in the brain cells or tissues of the patient.
- 34. The kit of claim 33, wherein the GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, comprises lithium or a salt thereof.
- 35. The kit of claim 33, further comprising a device for delivering the therapeutically effective composition, comprising the pharmaceutically acceptable GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, in an amount that is sufficient to block or inhibit activity of GSK-3 or GSK-3α, respectively.
- 36. The kit of claim 35, wherein the GSK-3 inhibitor or GSK-3α-specific inhibitor, respectively, comprises lithium or a salt thereof.
- 37. A method of detecting a composition of matter that blocks or inhibits GSK-3 kinase activity, comprising testing the composition in brain cells or brain tissue in vitro from a subject for its capability of blocking, reducing or inhibiting the processing of amyloid precursor proteins to beta-amyloid peptides of the type characterizing Alzheimer's disease and comparing the effectiveness of such composition for disrupting the production of the Aβ peptides with the effectiveness of lithium or other known GSK-3 inhibitors to do so, and selecting the composition having such effective blocking, inhibiting or reducing capability.
- 38. The method of claim 37, further comprising testing the composition in brain cells or brain tissue from a subject for GSK-3α specificity; and testing its capability of blocking, reducing or inhibiting γ-secretase mediated-APP processing, then comparing the effectiveness of such composition for disrupting APP processing with the effectiveness of lithium or other known GSK-3α inhibitors, and selecting the composition having such effective blocking, inhibiting or reducing capability.
- 39. The method of claim 38, further comprising testing the composition for its capability of blocking or inhibiting GSK-3β activity, and selecting the composition that blocks, inhibits or reduces GSK-3α activity without affecting GSK-3β activity.
REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to U.S. Provisional Application No. 60/359,290, filed Feb. 20, 2002, the content of which is herein incorporated by reference.
GOVERNMENT INTEREST
[0002] This invention was supported in part by Grant Nos. AGI 1542 and RO1MH58324 from the National Institutes of Health. Accordingly, the Government may have certain rights in this invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60359290 |
Feb 2002 |
US |