METHODS AND DEVICE TO NEUTRALIZE SOLUBLE TOXIC AGENTS IN THE BRAIN

• US 20080286330A1
• Filed: 05/14/2008
• Published: 11/20/2008
• Est. Priority Date: 05/14/2007
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Shafer, Lisa Lynn, Thakker, Deepak Ramesh
• Granted Patent: US 9,040,045 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• 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: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/54 F(ab')2

Abstract

Methods, agents and devices for treating a patient to reduce accumulation of certain proteins in the brain are described. Such proteins include Aβ, and the methods, agents and devices are useful for reducing the accumulation of Aβ, which is a principal constituent of the plaques associated with such diseases as Alzheimer'"'"'s disease (AD). Antibodies to Aβ, when delivered systemically or directly into the central nervous system, improve cognitive deficits in a transgenic mouse model of AD. However, unlike peripheral of antibodies to Aβ, which increased cerebral vascular plaques and hemorrhages, direct central administration did not result in such an increase cerebral vascular plaques and hemorrhages.

Claims

1. A method for treating Alzheimer'"'"'s disease in a subject in need thereof, comprising:

chronically delivering to the central nervous system of the subject an anti-Aβ

antibody in an amount effective to treat the disease,

wherein the subject experiences substantially no increase in cerebral vascular amyloid plaque formation due to the chronic delivery of the antibody.

2. The method of claim 1, wherein the chronically delivering the antibody comprises chronically delivering the antibody to cerebrospinal fluid of the subject.

3. The method of claim 1, wherein chronically delivering the antibody comprises delivering the antibody intracerebroventricularly.

4. The method of claims 1, wherein the antibody binds Aβ

42.

5. The method of claims 1, wherein the antibody binds Aβ

40.

6. The method of claims 1, wherein the antibody binds an intracellular Aβ

.

7. The method of claim 1, wherein the antibody comprises an immunoglobulin domain.

8. The method of claim 1, wherein the antibody is a F(ab′

)2 fragment.

9. The method of claim 1, further comprising implanting an infusion device in the subject, wherein chronically delivering the antibody to the central nervous system of the subject comprises delivering the antibody via the infusion device.

15. The method of claim 1, further comprising implanting an infusion device in the subject, wherein chronically delivering the antibody to the central nervous system of the subject comprises delivering the antibody via the infusion device.

10. A method for treating Alzheimer'"'"'s disease in a subject in need thereof, comprising:

chronically delivering to the central nervous system of the subject an anti-Aβ

antibody in an amount effective to treat the disease,

wherein the subject experiences substantially no increase in cerebral hemorrhage due to the chronic delivery of the antibody.

11. The method of claim 10, wherein the chronically delivering the antibody comprises chronically delivering the antibody to cerebrospinal fluid of the subject.

12. The method of claim 10, wherein chronically delivering the antibody comprises delivering the antibody intracerebroventricularly.

13. The method of claims 10, wherein the antibody binds Aβ

42.

14. The method of claim 10, wherein the antibody comprises an immunoglobulin domain.

16. A method for treating a subject having a cerebral vascular disease associated with increased or aberrant soluble Aβ

, amyloid fibrils, or amyloid plaques, comprising;

chronically delivering to the central nervous system of the subject an anti-Aβ

antibody in an amount effective to treat the disease.

17. The method of claim 16, wherein chronically delivering the antibody comprises delivering the antibody to cerebrospinal fluid of the subject.

18. The method of claim 16, wherein chronically delivering the antibody comprises delivering the antibody intracerebroventricularly.

19. The method of claim 16, wherein the disease is cerebral amyloid angiopathy.

20. The method of claim 16, further comprising implanting an infusion device in the subject, wherein chronically delivering the antibody to the central nervous system of the subject comprises delivering the antibody via the infusion device.

21. A method for treating a disease associated with increased or aberrant soluble Aβ

, amyloid fibrils, or amyloid plaques, comprising;

chronically delivering to the central nervous system of a subject in need thereof an anti-Aβ

antibody in an amount effective to treat the disease.

22. The method of claim 21, wherein chronically delivering the antibody comprises delivering the antibody to cerebrospinal fluid of the subject.

23. The method of claim 21 wherein chronically delivering the antibody comprises delivering the antibody intracerebroventricularly.

24. The method of claim 21, wherein the disease is Alzheimer'"'"'s Disease.

25. The method of claim 21, wherein the disease is Lewy body dementia.

26. The method of claim 21, wherein the disease is Down'"'"'s Syndrome.

27. The method of claim 21, wherein treating the disease comprises treating memory loss.

28. The method of claim 21, further comprising implanting an infusion device in the subject, wherein chronically delivering the antibody to the central nervous system of the subject comprises delivering the antibody via the infusion device.

29. A method for clearing Aβ

from the vasculature of a brain of a subject in need thereof, comprising;

chronically delivering to the central nervous system of the subject an anti-Aβ

antibody in an amount effective to clear the Aβ

.

30. The method of claim 29, wherein the chronically delivering the antibody comprises chronically delivering the antibody to cerebrospinal fluid of the subject.

31. The method of claim 29, wherein chronically delivering the antibody comprises delivering the antibody intracerebroventricularly.

32. The method of claim 29, wherein chronically delivering the antibody comprises delivering the antibody intraparenchymally.

33. The method of claim 29, further comprising implanting an infusion device in the subject, wherein chronically delivering the antibody to the central nervous system of the subject comprises delivering the antibody via the infusion device.