Treatment of maladaptive substance use with H-ras antagonists

• US 20070148660A1
• Filed: 06/14/2006
• Published: 06/28/2007
• Est. Priority Date: 06/16/2005
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Ron, Dorit
• Application Number:
  US11/453,560
• Publication Number:
  US 20070148660A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

The present invention provides a method of mitigating a symptom of maladaptive substance use in a subject by inhibiting H-ras. In addition, the invention provides a variety of prescreening and screening methods aimed at identifying agents that modulate a symptom of maladaptive substance use. Methods of the invention can involve assaying test agent binding to H-ras. Alternatively, test agents can be screened for their ability to alter the level of H-ras polypeptides, polynucleotides, or function. Finally, the invention also provides a diagnostic method that entails measuring one or more of these levels and determining risk for maladaptive substance use based on comparison to the corresponding level for a control population.

Claims

1. A method of mitigating a symptom of maladaptive substance use, the method comprising administering an effective amount of an inhibitor of H-ras to a subject, whereby the symptom of maladaptive substance use is mitigated.

2. The method of claim 1, wherein the substance comprises a drug selected from the group consisting of an opioid, a psychostimulant, a cannabinoid, an empathogen, a dissociative drug, and alcohol.

3. The method of claim 1, wherein the inhibitor comprises an antagonist that inhibits a function of H-ras.

4. The method of claim 1, wherein the symptom of maladaptive substance use is selected from the group comprising:

drug reward, incentive salience for a drug, drug craving, drug seeking, and drug consumption.

5. The method of claim 1, wherein the inhibitor is administered via implantation of a depot formulation comprising the inhibitor.

29. A kit comprising:

(a) an inhibitor of a H-ras in a pharmaceutically acceptable carrier;

(b) instructions for carrying out the method of claim 1.

6. A pharmaceutical composition comprising an inhibitor of H-ras;

and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition of claim 6, wherein the inhibitor comprises an antagonist that inhibits a function of H-ras.

8. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition comprises a depot formulation.

9. A method of prescreening for an agent that can modulate a symptom of maladaptive substance use in a subject, the method comprising:

(a) contacting a test agent with a H-ras;

(b) determining whether the test agent specifically binds to H-ras; and

(c) if the test agent specifically binds to H-ras, selecting the test agent as a potential modulator of a symptom of maladaptive substance use in a subject.

10. A method of prescreening for an agent that can modulate a symptom of maladaptive substance use in a subject, the method comprising:

(a) contacting a test agent with a polynucleotide encoding H-ras;

(b) determining whether the test agent specifically binds to the polynucleotide encoding H-ras; and

(c) if the test agent specifically binds to the polynucleotide encoding H-ras, selecting the test agent as a potential modulator of a symptom of maladaptive substance use in a subject.

11. (canceled)

12. (canceled)

13. A method of screening for an agent that can modulate a symptom of maladaptive substance use in a subject, the method comprising:

(a) contacting a test agent with a H-ras,

(b) determining whether the test agent acts as an agonist or an antagonist of H-ras;

(c) if the test agent acts as an agonist or antagonist of H-ras, selecting the test agent as a potential modulator of maladaptive substance use in a subject.

14. (canceled)

15. (canceled)

16. (canceled)

17. (canceled)

18. (canceled)

19. (canceled)

20. (canceled)

21. (canceled)

22. (canceled)

23. A method of screening for an agent that that can modulate maladaptive substance use in a subject, the method comprising:

(a) selecting a modulator of a H-ras as a test agent; and

(b) measuring the ability of the selected test agent to modulate a symptom of maladaptive substance use in an animal model.

24. (canceled)

25. (canceled)

26. (canceled)

27. A method of assessing a subject'"'"'s risk for maladaptive substance use, the method comprising determining the level of H-ras polypeptides, polynucleotides, or function in a biological sample from the subject, wherein risk for maladaptive substance use is directly correlated with said level.

30. A diagnostic kit comprising:

(a) a component that specifically binds to a H-ras polypeptide or polynucleotide; and

(b) instructions for carrying out the method of claim 27.

28. (canceled)