Active immunization for treatment of alzheimer's disease
View Patent ↗The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of Aβ and antibodies binding to the same.
1. A method for prophylaxis of Alzheimer's disease in a subject, comprising administering to the subject a dosage of an immunogenic fragment of Aβ (SEQ ID NO: 42) in a regime effective to produce an immune response comprising antibodies against Aβ, wherein at least one amino acid of the immunogenic fragment is a D amino acid, thereby effecting prophylaxis of said disease, wherein the dose of the Aβ is administered to the patient is at least 50 μg.
2. The method of claim 1 , further comprising administering an adjuvant with said peptide.
3. The method of claim 2 , wherein said adjuvant is selected from the group consisting of STIMULON QS-21, 3 De-O-acylated-monophosphoryl lipid A, and alum.
4. The method of claim 1 , wherein said Aβ fragment is Aβ 1-3.
5. The method of claim 1 , wherein said Aβ fragment is Aβ 1-4.
6. The method of claim 1 , wherein said Aβ fragment is Aβ 1-5.
7. The method of claim 1 , wherein said Aβ fragment is Aβ 1-6.
8. The method of claim 1 , wherein said Aβ fragment is Aβ 1-7.
9. The method of claim 1 , wherein said Aβ fragment is Aβ 1-12.
10. The method of claim 1 , wherein said Aβ fragment is Aβ 13-28.
11. The method of claim 1 , wherein said Aβ fragment is Aβ 25-35.
12. The method of claim 1 , wherein said Aβ fragment is Aβ 33-42.
13. The method of claim 4 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
14. The method of claim 5 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
15. The method of claim 6 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
16. The method of claim 7 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
17. The method of claim 8 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
18. The method of claim 9 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
19. The method of claim 10 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
20. The method of claim 11 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
21. The method of claim 12 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
22. The method of claim 1 , wherein the subject has a known genetic risk of Alzheimer's disease.
23. The method of claim 1 , wherein said subject is a human being.
24. A method for treating Alzheimer's disease in a subject, comprising administering to the subject a dosage of an immunogenic fragment of Aβ (SEQ ID NO: 42) in a regime effective to produce an immune response comprising antibodies against Aβ, wherein at least one amino acid of the immunogenic fragment is a D amino acid, thereby treating said disease, wherein the dose of the Aβ administered to the patient is at least 50 μg.
25. The method of claim 24 , further comprising administering an adjuvant with said peptide.
26. The method of claim 25 , wherein said adjuvant is selected from the group consisting of STIMULON QS-21, 3 De-O-acylated-monophosphoryl lipid A and alum.
27. The method of claim 24 , wherein said Aβ fragment is Aβ 1-3.
28. The method of claim 24 , wherein said Aβ fragment is Aβ 1-4.
29. The method of claim 24 , wherein said Aβ fragment is AP 1-5.
30. The method of claim 24 , wherein said Aβ fragment is Aβ 1-6.
31. The method of claim 24 , wherein said Aβ fragment is Aβ 1-7.
32. The method of claim 24 , wherein said Aβ fragment is Aβ 1-12.
33. The method of claim 24 , wherein said Aβ fragment is Aβ 13-28.
34. The method of claim 24 , wherein said Aβ fragment is Aβ 25-35.
35. The method of claim 24 , wherein said Aβ fragment is Aβ 33-42.
36. The method of claim 27 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
37. The method of claim 28 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
38. The method of claim 29 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
39. The method of claim 30 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
40. The method of claim 31 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
41. The method of claim 32 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
42. The method of claim 33 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
43. The method of claim 34 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
44. The method of claim 35 , wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.
45. The method of claim 24 , wherein the subject has a known genetic risk of Alzheimer's disease.
46. The method of claim 24 , wherein said subject is a human being.