Peptide conjugate compositions and methods for the prevention and treatment of alzheimer's disease

Abstract

The invention provides compositions and methods for the treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient, such as Alzheimer's disease. Such methods entail administering an immunogenic fragment of Aβ, lacking a T-cell epitope, capable of inducing a beneficial immune response in the form of antibodies to Aβ. In another aspect, the immunogenic fragment of Aβ is capable of elevating plasma Aβ levels. The immunogenic fragments comprise linear or multivalent peptides of Aβ. Pharmaceutical compositions comprise the immunogenic fragment chemically linked to a carrier molecule which may be administered with an adjuvant.

1 - 18 . (canceled) 
     
     
         19 . A method for preventing or treating a disease associated with amyloid deposits of Aβ in the brain of a patient comprising administering an effective dose of a composition comprising a multivalent branched multiple antigen peptide (MAP) linked to a carrier to form a conjugate, wherein the MAP comprises two or more non-identical immunogenic linear 8 amino acid peptide fragments (8-mers) of Aβ, each fragment lacking a T-cell epitope, and wherein one of said 8-mers is Aβ 21-28 (AEDVGSNK) (SEQ ID NO: 22). 
     
     
         20 . The method of  claim 19  wherein one of the immunogenic fragments of Aβ is selected from the group consisting of an 8-mer corresponding to amino acid regions Aβ 1-8, Aβ 2-9, Aβ 3-10, Aβ 7-14, Aβ 17-24, Aβ 21-28, and Aβ 33-40. 
     
     
         21 . The method of  claim 19  wherein the MAP is selected from the group consisting of amino acid regions a) Aβ 1-8 and Aβ 21-28, b) Aβ 3-10 and Aβ 21-28, c) Aβ 7-14 and Aβ 21-28 and Aβ 3-10, and d) Aβ 7-14 and Aβ 33-40 and Aβ 21-28 and Aβ 3-10, wherein each of the 8-mers are linked together. 
     
     
         22 . The method of  claim 21  wherein the MAP comprises the 8-mers Aβ 3-10 and Aβ 21-28 linked together on a lysine-based scaffold. 
     
     
         23 . The method of  claim 19  wherein the carrier is selected from the group consisting of serum albumin, keyhole limpet hemocyanin (KLH), an immunoglobulin, a tetanus toxoid protein, a bacterial toxoid protein, and an attenuated toxin derivative. 
     
     
         24 . The method of  claim 22  wherein the carrier is the outer membrane protein complex of  Neisseria meningitidis  (OMPC). 
     
     
         25 . A method for preventing or treating a disease associated with amyloid deposits of Aβ in the brain of a patient, comprising administering an effective dose of a pharmaceutical composition, comprising the MAP of  claim 19 , and a pharmaceutically acceptable adjuvant. 
     
     
         26 . The method of  claim 25  wherein the pharmaceutically acceptable adjuvant is selected from the group consisting of an aluminum salt, alum, a lipid, and a saponin-based adjuvant. 
     
     
         27 . A method for preventing or treating a disease associated with amyloid deposits of Aβ in the brain of a patient comprising administering an effective dose of a pharmaceutical composition comprising a MAP linked to a carrier to form a conjugate, wherein the MAP comprises the 8-mers Aβ 3-10 and Aβ 21-28 linked together on a lysine-based scaffold and the carrier is OMPC, and a saponin-based adjuvant.