Active immunization of AScr for prion disorders
Disclosed are pharmaceutical compositions and methods for preventing or treating a number of amyloid diseases, including Alzheimer's disease, prion diseases, familial amyloid neuropathies and the like. The pharmaceutical compositions include immunologically reactive amounts of amyloid fibril components, particularly fibril-forming peptides or proteins. Also disclosed are therapeutic compositions and methods which use immune reagents that react with such fibril components.
1. A method of treating a prior disorder associated with AScr in a mammalian subject suffering from the disorder, comprising administering to the subject a dosage of an agent effective to produce an immune response comprising antibodies against the agent and an adjuvant that augments the immune response to the agent, and thereby treating the disorder, wherein the agent is PrR or AScr.
2. The method of claim 1 , wherein the agent is AScr.
3. The method of claim 1 , wherein said agent is PrP.
4. The method of claim 1 , wherein said agent is a peptide linked to a carrier molecule.
5. The method of claim 1 , wherein said adjuvant is selected from the group consisting of QS21, monophosphoryl lipid, and alum.
6. The method of claim 1 , wherein said immune response is characterized by a serum titer of the antibodies of at least 1:1000 with respect to the agent.
7. The method of claim 6 , wherein said serum titer of the antibodies is at least 1:5000 with respect to the agent .
8. The method of claim 1 , wherein said immune response is characterized by a serum titer of the antibodies against the agent corresponding to greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample.
9. The method of claim 8 , wherein said serum titer of the antibodies is measured at a serum dilution of about 1:100.
10. The method of claim 3 , wherein the agent is selected from the following PrP genetic variants: Leu102, Val167, Asn178, and Lys200.