Claims
- 1. A method for diagnosing occurrence of a stroke or assessing a patient's susceptibility to a stroke, the method comprising detecting in a patient sample an elevated level of UCP-2 expression.
- 2. The method of claim 1, wherein detection comprises detecting an elevated level of UCP-2 transcript.
- 3. The method of claim 2, wherein detection comprises probing the sample with a nucleic acid probe that is homologous to at least 15 consecutive nucleotides of a UCP-2 sequence and determining the amount of nucleic acid bound by the probe.
- 4. The method of claim 1, wherein detection comprises detecting an elevated level of a UCP-2 polypeptide.
- 5. The method of claim 4, wherein detection comprises assaying for the presence of the UCP-2 polypeptide by contacting the sample with an antibody that specifically binds to the UCP-2 polypeptide to form a complex and detecting the complex.
- 6. The method of claim 5, wherein detection comprises performing an ELISA.
- 7. The method of claim 1, wherein the stroke is an ischemic stroke.
- 8. A method for assessing a patient's risk of having a stroke comprising comparing the level of UCP-2 expression in a test sample from the patient with a baseline value, wherein an elevated level of UCP-2 expression in the patient sample relative to the baseline indicates that the patient is at risk for stroke.
- 9. The method of claim 8, wherein the baseline value is the level of UCP-2 expression in a patient sample obtained prior to the test sample.
- 10. The method of claim, 8, wherein the baseline value is an average or mean value for UCP-2 expression in a population of control individuals.
- 11. A method for treating a subject having or being susceptible to a neurological disorder or a neuronal injury, the method comprising administering to the subject an effective amount of an agent that increases the activity of UCP-2.
- 12. The method of claim 11, wherein the neuronal injury is a stroke.
- 13. The method of claim 12, wherein the neuronal injury is an ischemic stroke.
- 14. The method of claim 11, wherein the neurological disorder is selected from the group consisting of Parkinson's disease, Huntington's disease, inherited ataxias, motor neuron diseases, Alzheimer's disease, epilepsy, and traumatic brain injury.
- 15. The method of claim 11, wherein the subject is susceptible to the neurological disorder or the neuronal injury, and the subject is administered a prophylactic amount of the agent prior to occurring of the neurological disorder or the neuronal injury.
- 16. The method of claim 11, wherein the subject has the neurological disorder or the neuronal injury, and the subject is administered a therapeutic amount of the agent.
- 17. The method of claim 11, wherein the agent is administered in combination with a secondary agent that increases the permeability of the blood/brain barrier.
- 18. The method of claim 17, wherein the secondary agent is selected from the group consisting of bradykinin, serotonin, histamine and arachidonic acid.
- 19. The method of claim 11, wherein the agent is administered in combination with an anticoagulant.
- 20. The method of claim 11, wherein the agent is a purified UCP-2 polypeptide in combination with a pharmaceutically acceptable carrier.
- 21. The method of claim 11, wherein the agent is an agent other than UCP-2.
- 22. The method of claim 21, wherein the agent stimulates the synthesis or expression of UCP-2 or any other UCP-2 inducer.
- 23. The method of claim 21, wherein the agent comprises a nucleic acid that encodes UCP-2 or any other UCP-2 inducer.
- 24. The method of claim 23, wherein the agent comprises a vector that contains the nucleic acid that encodes UCP-2.
- 25. The method of claim 24, wherein the vector is a viral vector.
- 26. The method of claim 25, wherein the viral vector is an adenoviral vector.
- 27. The method of claim 26, wherein the vector further comprises a promoter operably linked with the nucleic acid that encodes UCP-2, the promoter selectively driving expression of UCP-2 or a UCP-2 inducer in nerve cells.
- 28. The method of claim 27, wherein the nerve cells are cortical neuron cells, hippocampal neuron cells or neuronal cells in any other brain region affected by a stroke.
- 29. The method of claim 25, wherein the viral vector is introduced into the cerebrospinal fluid.
- 30. The method of claim 25, wherein the viral vector is introduced into the intraventricular space.
- 31. The method of claim 24, further comprising producing ex vivo genetically-modified neuronal or non-neuronal stem cells that harbor a vector that includes a nucleic acid encoding for UCP-2, and wherein administering comprises introducing the modified stem cells into the intracerebroventricular space or into the cerebrospinal fluid.
- 32. A method for screening for an agent useful for treating a neurological disorder or a neuronal injury, the method comprising identifying an agent that upregulates UCP-2 expression and/or activity.
- 33. The method of claim 32, wherein the neuronal injury is stroke.
- 34. The method of claim 32, wherein the neurological disorder is selected from the group consisting of Parkinson's disease, Huntington's disease, inherited ataxias, motor neuron diseases, Alzheimer's disease, epilepsy, and traumatic brain injury.
- 35. The method of claim 32, wherein the method further comprises:
(a) administering to a test subject a test compound, wherein the test subject is a mammal other than a human; (b) preconditioning the test subject; and (c) determining in a sample from the test subject the expression level of UCP-2 to identify a test agent that upregulates UCP-2 expression in the test subject.
- 36. The method of claim 35, wherein the test and control subject is a rat.
- 37. A method of screening for an agent useful for treating a neurological disorder or a neuronal injury, the method comprising identifying an agent that inhibits cellular apoptosis.
- 38. The method of claim 37, wherein the neuronal injury is stroke.
- 39. The method of claim 37, wherein the neuronal injury is ischemic stroke.
- 40. The method of claim 37, wherein the neurological disorder is selected from the group consisting of Parkinson's disease, Huntington's disease, inherited ataxias, motor neuron diseases, Alzheimer's disease, epilepsy, and traumatic brain injury.
- 41. The method of claim 37, wherein the agent inhibits the loss of mitochondrial membrane potential.
- 42. The method of claim 37, wherein the agent inhibits cytochrome c release from mitochondria.
- 43. The method of claim 37, wherein the agent inhibits caspase 3 activation.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority from U.S. Provisional Patent Application Serial No. 60/244,946, filed Nov. 1, 2000, the full disclosures of which are incorporated herein by reference in their entirety for all purposes.
Provisional Applications (1)
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Number |
Date |
Country |
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60244946 |
Nov 2000 |
US |