AGENTS THAT REDUCE APOE-INDUCED IMPAIRMENT OF MITOCHONDRIA AND METHODS OF USE THEREOF

• US 20090082271A1
• Filed: 12/07/2006
• Published: 03/26/2009
• Est. Priority Date: 12/07/2005
• Status: Abandoned Application

• Current Assignee: The J. David Gladstone Institutes
• Original Assignee: The J. David Gladstone Institutes
• Inventors: Huang, Yadong, Mahley, Robert W.
• Application Number:
  US12/092,550
• Publication Number:
  US 20090082271A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

The present invention provides isolated cells comprising a nucleic acid encoding a toxic form of apoE. The present invention further provides screening methods for identifying compounds that reduce apoE-induced impairment of mitochondrial integrity and/or function. The present invention further provides kits for use in carrying out a subject screening method. The present invention provides agents that reduce apoE-induced impairment of mitochondrial integrity and/or function; and use of such agents in the treatment of apoE-related disorders.

Claims

1. A pharmaceutical composition comprising:

a) an agent that reduces apolipoprotein E4 (apoE4) neurotoxic polypeptide-induced impairment of mitochondrial integrity and/or function; and

b) a pharmaceutically acceptable carrier.

2. The composition of claim 1, wherein the agent is a sodium channel blocker.

3. The composition of claim 1, wherein the composition is formulated for oral administration.

4. The composition of claim 1, wherein the composition is formulated for administration by inhalation.

5. The composition of claim 1, wherein the composition is formulated for administration by injection.

6. A method of treating an apolipoprotein E4 (apoE4)-associated disorder in an individual, the method comprising administering to an individual in need thereof an effective amount of an agent that reduces apoE4-induced impairment of mitochondrial integrity and/or function.

7. The method of claim 6, wherein the agent is a peptide comprising a neuroprotective carboxyl-terminal fragment of apoE4.

8. The method of claim 6, wherein the agent is a sodium channel blocker.

9. The method of claim 6, wherein the apoE4-associated disorder is Alzheimer'"'"'s disease.

10. The method of claim 6, wherein the agent is administered intravenously.

11. The method of claim 6, wherein the agent is administered orally.

12. The method of claim 6, wherein the agent is administered by continuous delivery.

13. A method of treating Alzheimer'"'"'s disease in an individual, the method comprising administering to an individual having Alzheimer'"'"'s disease an effective amount of an agent that reduces apoE4-induced impairment of mitochondrial integrity and/or function.

14. The method of claim 13, wherein the agent is a sodium channel blocker.

15. The method of claim 13, wherein the agent is administered intravenously.

16. The method of claim 13, wherein the agent is administered orally.

17. The method of claim 13, wherein the agent is administered by continuous delivery.