TREATMENT AND DIAGNOSIS OF ALZHEIMER'S DISEASE

• US 20010014670A1
• Filed: 01/08/1999
• Published: 08/16/2001
• Est. Priority Date: 01/09/1998
• Status: Active Grant

• Current Assignee: Intracell, LLC
• Original Assignee: Abrams J. Todd, Brian J. Balin
• Inventors: HUDSON, ALAN P., BALIN, BRIAN J., ABRAMS, J. TODD, WHITTUM-HUDSON, JUDITH A.
• Granted Patent: US 7,189,703 B2
• Time in Patent Office: Days
• US Class Current: 514/29
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07K 16/125 from Chlamydiales (O)
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: G01N 2333/295 from Chlamydiales (o)
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease
• CPC Class Codes: Y10S 436/811 Test for named disease, body condition or organ function

Abstract

The invention relates to a method of treating Alzheimer'"'"'s disease in a mammal comprising administering to the mammal an anti-microbial agent having anti-Chlamydia pneumoniae activity. The invention also relates to a method of diagnosing Alzheimer'"'"'s disease in a mammal comprising measuring the serum anti-Chlamydia pneumoniae antibody titer in a patient suspected of having Alzheimer'"'"'s disease.

Claims

1. A method of treating a Chlamydia pneumoniae infection of the central nervous system of a mammal, wherein said mammal does not exhibit symptoms of multiple sclerosis or meningoencephalitis, said method comprising administering to said mammal an anti-microbial agent having anti-Chlamydia pneumoniae activity wherein said anti-microbial agent inhibits infection of cells or inhibits growth or replication of said Chlamydia pneumoniae in said mammal, thereby treating said Chlamydia pneumoniae infection.

2. The method of

claim 1

, wherein said anti-microbial agent is an antibiotic.

3. The method of

claim 2

, wherein said antibiotic is selected from the group consisting of a fluoroquinolone, a sulfonamide, a tetracycline, and a macrolide antibiotic.

4. The method of

claim 3

, wherein said antibiotic is selected from the group consisting of ciprofloxacin, ofloxacin, sulfamethoxazole, trimethoprim, doxycycline, minocycline, oxytetracycline, tetracycline, azithromycin, clarithromycin, dirithromycin, erythromycin and troleandomycin.

5. The method of

claim 4

, wherein said antibiotic is selected from the group consisting of azithromycin and doxycycline.

6. The method of

claim 1

, wherein said mammal is a human.

7. The method of

claim 6

, wherein said anti-microbial agent is administered to said human by a route selected from the group consisting of orally, systemically, intranasally and intrathecally.

8. A method of treating Alzheimer'"'"'s disease in a mammal, said method comprising administering to said mammal an anti-microbial agent having anti-Chlamydia pneumoniae activity wherein said anti-microbial agent inhibits infection of cells or inhibits growth or replication of said C. pneumoniae in said mammal, thereby treating said Alzheimer'"'"'s disease.

9. The method of

claim 8

, wherein said anti-microbial agent is an antibiotic.

10. The method of

claim 9

, wherein said antibiotic is selected from the group consisting of a fluoroquinolone, a sulfonamide, a tetracycline, and a macrolide antibiotic.

11. The method of

claim 10

, wherein said antibiotic is selected from the group consisting of ciprofloxacin, ofloxacin, sulfamethoxazole, trimethoprim, doxycycline, minocycline, oxytetracycline, tetracycline, azithromycin, clarithromycin, dirithromycin, erythromycin and troleandomycin.

12. The method of

claim 11

, wherein said antibiotic is selected from the group consisting of azithromycin and doxycycline.

13. The method of

claim 8

, wherein said mammal is a human.

14. The method of

claim 13

, wherein said anti-microbial agent is administered to said human by a route selected from the group consisting of orally, systemically, intranasally and intrathecally.

15. A method of treating Alzheimer'"'"'s disease in a human patient, said method comprising administering to said mammal an anti-microbial agent having anti-Chlamydia pneumoniae activity, wherein said anti-microbial agent inhibits infection of cells or inhibits growth or replication of said C. pneumoniae in said mammal, said method further comprising administering to said patient an anti-inflammatory agent, thereby treating said Alzheimer'"'"'s disease.

16. The method of

claim 15

, wherein said anti-inflammatory agent is a non-steroidal anti-inflammatory agent.

17. The method of

claim 15

, wherein said anti-inflammatory agent is selected from the group consisting of ibuprofen, phenylbutazone, indomethacin, sulindac, diclofenac, piroxicam, naproxen, ketoprofen, pirprofen, flurbiprofen, tiaprofenic acid, tolfenamic acid, and a COX-2 inhibitor.

18. A method of diagnosing Alzheimer'"'"'s disease in a human patient suspected of having Alzheimer'"'"'s disease, wherein said human does not exhibit symptoms of multiple sclerosis or menginoencephalitis, said method comprising obtaining a cerebrospinal fluid sample from said patient, determining whether said cerebral spinal fluid sample contains Chlamydia pneumoniae, wherein the presence of Chlamydia pneumoniae in said sample is an indication that said patient has Alzheimer'"'"'s disease.

19. A method of diagnosing Alzheimer'"'"'s disease in a human patient suspected of having Alzheimer'"'"'s disease, wherein said human does not exhibit symptoms of multiple sclerosis or menginoencephalitis, said method comprising measuring the serum anti-Chlamydia pneumoniae antibody titer in a patient suspected of having Alzheimer'"'"'s disease and comparing the serum anti-Chlamydia pneumoniae antibody titer in said patient with the mean serum anti-Chlamydia pneumoniae antibody titer in a population of control patients, wherein a higher serum anti-Chlamydia pneumoniae antibody titer in said patient compared with said mean serum anti-Chlamydia pneumoniae antibody titer is an indication that said patient has Alzheimer'"'"'s disease.

20. A method of diagnosing Alzheimer'"'"'s disease in a human patient, said method comprising administering an anti-SAF antibody to said human and determining whether said anti-SAF antibody binds to central nervous system tissue in said human, wherein binding of anti-SAF antibody to central nervous tissue in said human is an indication that said human has Alzheimer'"'"'s disease.

21. The method of

claim 20

, wherein said anti-SAF antibody is administered to said human intrathecally.

22. The method of

claim 21

, wherein said antibody is labeled with a detectable label and wherein binding of said antibody is assessed by detecting said label bound to said tissue.

23. An anti-SAF antibody molecule.

25. An ELISA kit comprising an anti-SAF antibody and an instructional material.

24. The anti-SAF antibody molecule of

claim 25

, wherein said antibody is selected from the group consisting of a monoclonal antibody and a synthetic antibody.

26. A method of diagnosing Alzheimer'"'"'s disease in a human patient, said method comprising detecting evidence of the presence of C. pneumoniae in an intranasal sample obtained from said patient, wherein when the presence of C. pneumoniae in said sample is an indication that said patient has Alzheimer'"'"'s disease.

27. A method of identifying a candidate compound for treatment of Alzheimer'"'"'s disease comprising incubating cells infected with Chlamydia pneumoniae in the presence or absence of a test compound and measuring the level of replication of said Chlamydia pneumoniae in said cells, wherein a lower level of replication of said Chlamydia pneumoniae in the presence of said test compound compared with the level of replication of said Chlamydia pneumoniae in the absence of said test compound, is an indication that said test compound is a candidate compound for treatment of Alzheimer'"'"'s disease.

28. The method of

claim 27

, wherein said cells are selected from the group consisting of monocytes/microglia, macrophages, oligodendroglia, astroglial and neuronal cells.

29. A neuronal cell infected with Chlamydia pneumoniae.

30. A plurality of neuronal cells infected with Chlamydia pneumoniae.