METHODS FOR DETECTING SLEEPINESS

• US 20070105180A1
• Filed: 11/09/2006
• Published: 05/10/2007
• Est. Priority Date: 11/09/2005
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Seugnet, Laurent, Shaw, Paul, Boero, Jaime, Duntley, Stephen
• Granted Patent: US 7,915,005 B2
• Time in Patent Office: Days
• US Class Current: 435/22
• CPC Class Codes: C12Q 1/40 involving amylase
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/2864 Sleep disorders

Abstract

The invention generally provides a biomarker for sleepiness, a method for detecting sleepiness, and a method of identifying nucleic acids associated with sleepiness.

Claims

1. A method for detecting sleepiness in a subject, the method comprising measuring the level of amylase in the subject, wherein an elevated level of amylase compared to a baseline level of amylase indicates sleepiness.

2. The method of claim 1, wherein amylase is measured in a biosample taken from the subject.

3. The method of claim 2, wherein the biosample is selected from the group consisting a blood sample, an interstitial fluid sample, a saliva sample, a urine sample, and a pancreatic sample.

4. The method of claim 2, wherein the biosample is a saliva sample.

5. The method of claim 1, wherein the level of amylase measured is selected from the group consisting of the level of amylase mRNA, the level of amylase transcription, the level of amylase translation, the level of amylase protein, and the level of amylase activity.

6. The method of claim 1, wherein the level of amylase mRNA is measured.

7. The method of claim 1, wherein the subject has been diagnosed as having a sleep disorder.

8. The method of claim 1, wherein the subject is at risk for sleepiness.

9. The method of claim 8, wherein sleepiness is a condition selected from the group consisting of sleep deprivation, coma, dyssomnias, parasomnias, and sleep disorders.

28. The method of claim 1, further comprising identifying a difference in expression of a nucleic acid between the first nucleic acid expression profile and the second nucleic acid expression profile of at least two nucleic acid expression profile sets.

29. The method of claim 28, further comprising identifying a difference in expression of a nucleic acid between the first nucleic acid expression profile and the second nucleic acid expression profile of at least three nucleic acid expression profile sets.

10. A biomarker for sleepiness in a subject, the biomarker comprising the level of amylase in the subject.

11. The biomarker of claim 10, wherein an elevated level of amylase indicates sleepiness.

12. The biomarker of claim 10, wherein the level of amylase is selected from the group consisting of the level of amylase mRNA, the level of amylase transcription, the level of amylase translation, the level of amylase protein, and the level of amylase activity.

13. The biomarker of claim 12, wherein the level of amylase is the level of amylase mRNA.

14. The biomarker of claim 10, wherein the subject is at risk for sleepiness.

15. A method for identifying a nucleic acid sequence associated with sleepiness, the method comprising

(a) comparing a first nucleic acid expression profile and a second nucleic acid expression profile of a nucleic acid expression profile set, wherein the first nucleic acid expression profile and the second nucleic acid expression profile are selected from the group consisting of the following sets:

i. a first nucleic acid expression profile from a partially sleep resistant organism taken from at least one time point during resistance to sleep deprivation and a second nucleic acid expression profile of the partially sleep resistant organism taken from at least one time point during normal response to sleep deprivation,

ii. a first nucleic acid expression profile from an organism exposed to a pharmacological agent that increases waking and induces corresponding sleep compensation and a second nucleic acid expression profile from an organism exposed to a pharmacological agent that increases waking and does not induce corresponding sleep compensation, and

iii. a first nucleic acid expression profile from a sleep deprived organism with a corresponding activation of the homeostatic sleep response and a second nucleic acid expression profile from a sleep deprived organism without a corresponding activation of the homeostatic sleep response; and

(b) identifying a difference in the expression of a nucleic acid between the first nucleic acid expression profile and the second nucleic acid expression profile of a nucleic acid expression profile set, wherein a difference indicates that the nucleic acid is associated with sleepiness.

16. The method of claim 15, wherein the organisms are a single species selected from the group consisting of insects and mammals.

17. The method of claim 16, wherein the organisms are a single species selected from the genus Drosophila.

18. The method of claim 15, wherein nucleic acid expression is evaluated by a nucleic acid microarray or quantitative PCR.

19. The method of claim 15, wherein the organism is partially resistant to sleep because of the expression of a variant circadian clock gene.

20. The method of claim 15, wherein the at least one timepoint during sleep resistance is selected after about 0.5 to about 6 hours of sleep deprivation.

21. The method of claim 15, wherein the at least one timepoint during normal response is selected after about eight to about twelve hours of sleep deprivation.

22. The method of claim 15, wherein the pharmacological agent that increases waking and induces corresponding sleep compensation is caffeine.

23. The method of claim 15, wherein the pharmacological agent that increases waking and does not induce corresponding sleep compensation is methamphetamine.

24. The method of claim 15, wherein the sleep deprivation that does not activate a corresponding homeostatic sleep response is induced by starvation.

25. The method of claim 15, wherein the sleep deprivation that activates a corresponding homeostatic sleep response is selected from the group comprising mechanical or physical sleep disruption.

26. The method of claim 15, wherein the sleep deprived organism with or without a corresponding activation of the homeostatic sleep response is a sleep sensitive organism.

27. The method of claim 26, wherein the organism is sleep sensitive because of the expression of a variant circadian clock gene.