Methods and compostions for the treatment and/or diagnosis of neurological diseases and disorders

• US 20020052311A1
• Filed: 03/15/2001
• Published: 05/02/2002
• Est. Priority Date: 09/03/1999
• Status: Abandoned Application

• Current Assignee: Ramot University Authority For Applied Research and Industrial Development Limited
• Original Assignee: Ramot University Authority For Applied Research and Industrial Development Limited
• Inventors: Solomon, Beka, Frenkel, Dan
• Application Number:
  US09/808,037
• Publication Number:
  US 20020052311A1
• Time in Patent Office: Days
• US Class Current: 514/2
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/543 intranasal
• CPC Class Codes: A61K 2039/6075 Viral proteins
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/74 Inducing cell proliferation
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

A method of immunizing against plaque forming diseases using display technology is provided. The method utilize novel agents, or pharmaceutical compositions for vaccination against plaque forming diseases which rely upon presentation of an antigen or epitope on a display vehicle. The method further includes agents, or pharmaceutical compositions for vaccination against plaque forming diseases, which rely upon presentation of an antibody, or an active portion thereof, on a display vehicle. Whether antigens or antibodies are employed, disaggregation of plaques results from the immunization. The methods of the present invention also generally relates to treating and/or diagnosing neurological diseases and disorders of the central nervous, regardless of whether the disease or disorder is plaque-forming or non-plaque forming.

Claims

1. A method of treating a neurological disease or disorder of the central nervous system (CNS), comprising:

displaying a therapeutic molecule capable of treating the neurological disease or disorder of the CNS on a viral display vehicle; and

introducing the viral display vehicle into a subject in need thereof by applying an effective amount of the viral display vehicle displaying the therapeutic molecule to an olfactory system of the subject to treat the neurological disease or disorder.

2. The method of claim 1, wherein the neurological disease or disorder of the CNS is a plaque-forming disease or disorder.

3. The method of claim 2, wherein the plaque forming disease or disorder is selected from the group consisting of early onset Alzheimer'"'"'s disease, late onset Alzheimer'"'"'s disease, presymptomatic Alzheimer'"'"'s disease, SAA amyloidosis, hereditary Icelandic syndrome, senility and multiple myeloma.

4. The method of claim 2, wherein the plaque forming disease or disorder is selected from the group consisting of scrapie, bovine spongiform encephalopathy (BSE), kuru, Creutzfeldt-Jakob Disease (CJD), Gerstmann-Streussler-Sheinker Disease (GSS) and fatal familial insomnia (FFI).

5. The method of claim 2, wherein the therapeutic molecule displayed on the viral display vehicle is a polypeptide comprising an immunological portion of an antibody that binds at least one epitope of an aggregating protein associated with plaque formation in the plaque-forming disease or disorder, the binding of the immunological portion of the antibody to the aggregating protein being capable of disaggregating the aggregating protein and/or of preventing or inhibiting aggregation of the aggregating protein.

6. The method of claim 5, wherein the aggregating protein is selected from the group consisting of beta-amyloid, serum amyloid A, cystantin C, IgG kappa light chain, and prion protein.

7. The method of claim 5, wherein the aggregating protein is prion protein and at least one epitope of the prion protein as the aggregating protein is defined by at least a portion of an amino sequence of SEQ ID NO:

25.

8. The method of claim 1, wherein the neurological disease or disorder of the CNS is a non-plaque-forming disease or disorder.

9. The method of claim 8, wherein the non-plaque-forming disease or disorder is selected from the group consisting of Huntington'"'"'s chorea, viral infections of the brain, brain tumors, lysosomal storage diseases which cause neurodegeneration and are manifested by enzyme deficiencies, and multiple sclerosis.

10. The method of claim 8, wherein the non-plaque-forming disease or disorder associated with the formation of Lewy bodies.

11. The method of claim 8, wherein the therapeutic molecule displayed on the viral display vehicle is a polypeptide comprising an immunological portion of an antibody that binds at least one epitope of a protein associated with the neurological disease or disorder to inhibit the activity or effect of the protein.

12. The method of claim 8, wherein the therapeutic molecule is displayed on the viral display vehicle via binding or chemical linkage to the surface of the viral display vehicle.

13. The method of claim 1, wherein the viral display vehicle is a filamentous bacteriophage.

14. The method of claim 13, wherein the filamentous bacteriophage is selected from the group consisting of fd, f88, f1, and M13.

16. The pharmaceutical composition of claim 15, wherein the viral display vehicle is a filamentous bacteriophage.

18. The method of claim 17, wherein the viral display vehicle further displays a targeting agent.

19. The method of claim 18, wherein the targeting agent is a ligand of a molecular epitope in the brain useful for diagnosis.

20. The method of claim 17, wherein the diagnostic agent is a radioisotope.

21. The method of claim 17, wherein the diagnostic agent is a contrast agent.

22. The method of claim 17, wherein the in vivo imaging is magnetic resonance imaging (MRI).

23. The method of claim 17, wherein the neurological disease or disorder is a plaque-forming disease or disorder.

24. The method of claim 23, wherein the plaque-forming disease or disorder is Alzheimer'"'"'s disease.

25. The method of claim 24, wherein the targeting agent is selected from the group consisting of Chrysamine-G and a polypeptide comprising an immunological portion of an antibody that binds at least one epitope of beta-amyloid.

26. The method of claim 23, wherein the plaque-forming disease or disorder is associated with the presence of a scrapie isoform (PrP^sc) of prion protein in plaques.

27. The method of claim 26, wherein the targeting agent is a polypeptide comprising an immunological portion of an antibody that binds at least one epitope of prior protein.

28. The method of claim 17, wherein the viral display vehicle is a filamentous bacteriophage.

29. The method of claim 28, wherein the filamentous bacteriophage is selected from the group consisting of fd, f88, f1, and M13.

15. A pharmaceutical composition for treating a neurological disease or disorder of the central nervous system (CNS), comprising a pharmaceutically acceptable carrier and an effective amount of a viral display vehicle displaying a therapeutic molecule and being capable of treating a neurological disease or disorder of the CNS.

17. A method of diagnosing the presence or extent of a neurological disease or disorder of the central nervous system (CNS) by in vivo imaging, comprising:

displaying on a viral display vehicle a diagnostic agent capable of being detected by in vivo imaging;

introducing the viral display vehicle into a subject by applying the viral display vehicle displaying the diagnostic agent to an olfactory system of the subject; and

detecting the displayed diagnostic agent in the subject by in vivo imaging to diagnose the presence or extent of the neurological disease or disorder.

30. A pharmaceutical composition for diagnosing the presence or extent of a neurological disease or disorder of the central nervous system, comprising a pharmaceutically acceptable carrier and an effective amount of a viral display vehicle which displays a diagnostic agent capable of being detected by in vivo imaging.

31. The pharmaceutical composition of claim 30, wherein the viral display vehicle further displays a targeting agent.

32. The pharmaceutical composition of claim 30, wherein the viral display vehicle is a filamentous bacteriophage.