Compositions and methods for treating neurological disorders and diseases

• US 20040226056A1
• Filed: 02/09/2004
• Published: 11/11/2004
• Est. Priority Date: 12/22/1998
• Status: Abandoned Application

• Current Assignee: Myriad Genetics, Inc.
• Original Assignee: Myriad Genetics, Inc.
• Inventors: Roch, Jean-Marc, Bartel, Paul, Heichman, Karen
• Application Number:
  US10/776,013
• Publication Number:
  US 20040226056A1
• Time in Patent Office: Days
• US Class Current: 800/12
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The present invention generally relates to methods and compositions for treating neurological disorders and diseases. In addition, methods for selecting therapeutic agents useful for treating neurological disorders and diseases are provided.

Claims

1. A method of selecting agents that are potentially useful for the treatment of Alzheimer'"'"'s disease, comprising the steps of:

contacting focal adhesion kinase 2 with a test agent;

measuring a biological activity related to focal adhesion kinase 2 function in the presence and absence of said test agent; and

comparing the difference in the measured biological activity in the presence and absence of said test agent,

wherein a difference indicates the test agent is potentially useful for the treatment of Alzheimer'"'"'s disease.

2. The method of claim 1, wherein said biological activity is selected from the group consisting of:

the binding of focal adhesion kinase 2, or fragments and homologues thereof, to a protein that interacts with focal adhesion kinase 2, or fragments and homologues thereof;

the tyrosine kinase activity of focal adhesion kinase 2;

autophosphorylation of tyrosine residue 402 of focal adhesion kinase 2;

phosphorylation of tyrosine residue 579 of focal adhesion kinase 2;

phosphorylation of tyrosine residue 580 of focal adhesion kinase 2; and

phosphorylation of tyrosine residue 881 of focal adhesion kinase 2.

3. The method of claim 1 further comprising the step of determining whether the test agent reduces the level of Aβ

₄₂ produced in a cells or tissues.

4. The method of claim 1, wherein said contacting step comprises contacting said test agent with a cell expressing focal adhesion kinase 2.

5. The method of claim 4 further comprising the step of determining whether the test agent reduces the level of Aβ

₄₂ produced in said cell.

6. A method of treating or delaying the onset of Alzheimer'"'"'s disease in an individual in need of such treatment, comprising inhibiting focal adhesion kinase 2 in said individual by administering to said individual an inhibitor of focal adhesion kinase 2.

7. The method of claim 6, wherein said inhibitor reduces the level of a focal adhesion kinase 2 biological activity.

8. The method of claim 7, wherein said inhibitor is an antagonist of focal adhesion kinase 2 kinase activity.

9. The method of claim 6, wherein said inhibitor reduces the amount of mRNA transcript encoding focal adhesion kinase 2 or the amount of focal adhesion kinase 2.

10. The method of claim 8, wherein said inhibitor is selected from the group consisting of ribozymes, antisense oligonucleotides, siRNAs, and combinations thereof.

11. A method of reducing Aβ

₄₂ in an individual in need of such treatment, comprising inhibiting focal adhesion kinase 2 in said individual by administering to the individual an Aβ

₄₂-reducing effective amount of an inhibitor of focal adhesion kinase 2.

12. The method of claim 11, wherein the level of Aβ

₄₂ in the cerebrospinal fluid and/or plasma of the individual is reduced.

13. The method of claim 11, wherein said inhibitor reduces the level of a focal adhesion kinase 2 biological activity.

14. The method of claim 13, wherein said inhibitor is an antagonist of focal adhesion kinase 2 kinase activity.

15. The method of claim 14, wherein said inhibitor is selected from the group consisting of ribozymes, antisense oligonucleotides, siRNAs, and combinations thereof.

16. A method of diagnosis or prognosis of Alzheimer'"'"'s disease in an individual, comprising determining the level or activity of focal adhesion kinase 2 in said individual.

17. The method of claim 16, wherein the method is used for monitoring the effect of an Alzheimer'"'"'s disease treatment regimen, or for monitoring the progression of Alzheimer'"'"'s disease in the individual.

18. An isolated protein complex comprising a first protein interacting with a second protein, wherein said first protein is (1) focal adhesion kinase 2;

(2) a focal adhesion kinase 2 fragment;

(3) a fusion protein comprising (1) or (2);

or (4) a focal adhesion kinase 2 homologue having an amino acid sequence at least 75% identical to (1) or (2); and

wherein second protein is selected from the group consisting of focal adhesion kinase 2, ATP-binding cassette transporter, sub-family C, member 8, and delta-catenin, and fragments, and homologues thereof, and fusion protein thereof.

19. A method of selecting agents that are potentially useful for the treatment of Alzheimer'"'"'s disease, comprising the steps of:

contacting the isolated protein complex of claim 18 with a test agent;

detecting the protein complex;

comparing the level of the protein complex in the presence or absence of the test agent, wherein a difference indicates the test agent is potentially useful for the treatment of Alzheimer'"'"'s disease.