Prevention and treatment of amyloidogenic disease

Abstract

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 - 57 . (canceled) 
     
     
         58 . A method of therapeutically treating an amyloid disease in a patient, which disease is characterized by the presence of islet amyloid polypeptide (AIAPP) fibrils, comprising administering to the patient AIAPP or islet amyloid polypeptide precursor (IAPP) or a fragment thereof, which effects an immune response comprising antibodies against AIAPP. 
     
     
         59 . The method of  claim 58 , wherein the islet amyloid polypeptide (AIAPP) fibrils are in amyloid deposits in pancreatic islet cells. 
     
     
         60 . The method of  claim 58 , wherein the amyloid disease is diabetes type II or insulinoma. 
     
     
         61 . The method of  claim 58 , wherein the AIAPP, IAPP, or a fragment of AIAPP or IAPP, is linked to a carrier molecule. 
     
     
         62 . The method of  claim 61 , wherein the carrier molecule is a T-cell epitope. 
     
     
         63 . The method of  claim 61 , wherein the carrier molecule is a tetanus toxoid epitope. 
     
     
         64 . The method of  claim 61 , wherein the carrier molecule is a diphtheria toxoid epitope. 
     
     
         65 . The method of  claim 58 , wherein the immune response is characterized by a serum titer of the antibodies of at least 1:1000 with respect to AIAPP. 
     
     
         66 . The method of  claim 58 , wherein the immune response is characterized by a serum titer of the antibodies against AIAPP or IAPP that is greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample. 
     
     
         67 . The method of  claim 58 , further comprising the step of administering an adjuvant that augments the immune response. 
     
     
         68 . The method of  claim 67 , wherein the adjuvant is QS21, monophosphoryl lipid, or alum. 
     
     
         69 . The method of  claim 58 , whereby deposition of AIAPP fibril aggregates is inhibited. 
     
     
         70 . The method of  claim 58 , whereby AIAPP fibril aggregates are cleared. 
     
     
         71 . The method of  claim 58 , whereby progression of the amyloid disease is delayed. 
     
     
         72 . A method of reducing risk or delaying onset of an amyloid disease in a patient at risk of amyloid disease, which disease is characterized by the presence of AIAPP fibrils, comprising administering to the patient AIAPP or IAPP or a fragment thereof, which effects an immune response comprising antibodies against AIAPP. 
     
     
         73 . The method of  claim 72 , wherein the islet amyloid polypeptide (AIAPP) fibrils are in amyloid deposits in pancreatic islet cells. 
     
     
         74 . The method of  claim 72 , wherein the amyloid disease is diabetes type II or insulinoma. 
     
     
         75 . The method of  claim 58 , wherein the AIAPP, IAPP, or a fragment of AIAPP or IAPP, is linked to a carrier molecule. 
     
     
         76 . The method of  claim 75 , wherein the carrier molecule is a T-cell epitope. 
     
     
         77 . The method of  claim 75 , wherein the carrier molecule is a tetanus toxoid epitope. 
     
     
         78 . The method of  claim 75 , wherein the carrier molecule is a diphtheria toxoid epitope. 
     
     
         79 . The method of  claim 72 , wherein the immune response is characterized by a serum titer of the antibodies of at least 1:1000 with respect to AIAPP. 
     
     
         80 . The method of  claim 72 , wherein the immune response is characterized by a serum titer of the antibodies against AIAPP or IAPP that is greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample. 
     
     
         81 . The method of  claim 72 , further comprising the step of administering an adjuvant that augments the immune response. 
     
     
         82 . The method of  claim 81 , wherein the adjuvant is QS21, monophosphoryl lipid, or alum. 
     
     
         83 . The method of  claim 72 , whereby deposition of AIAPP fibril aggregates is inhibited. 
     
     
         84 . The method of  claim 72 , whereby AIAPP fibril aggregates are cleared. 
     
     
         85 . A method of therapeutically treating an amyloid disease in a patient, which disease is characterized by the presence of AIAPP fibrils comprising, administering to the patient an effective dosage of an antibody or fragment thereof that specifically binds to AIAPP to thereby treat the amyloid disease. 
     
     
         86 . The method of  claim 85 , wherein the islet amyloid polypeptide (AIAPP) fibrils are in amyloid deposits in pancreatic islet cells. 
     
     
         87 . The method of  claim 85 , wherein the amyloid disease is diabetes type II or insulinoma. 
     
     
         88 . The method of  claim 85 , wherein the antibody or antigen-binding fragment thereof binds to an aggregated amyloid fibril component with an affinity of greater than or equal to 10 6  M −1 . 
     
     
         89 . The method of  claim 85 , wherein the antibody or antigen-binding fragment thereof binds to a disaggregated amyloid fibril component with an affinity of less than 10 6  M −1 . 
     
     
         90 . The method of  claim 85 , wherein the antibody or antigen-binding fragment thereof binds to a precursor of an amyloid fibril component with an affinity of less than 10 6  M −1 . 
     
     
         91 . The method of  claim 85 , wherein the antibody is a human, chimeric, or humanized antibody. 
     
     
         92 . The method of  claim 91 , wherein the isotype of the antibody is human IgG1. 
     
     
         93 . The method of  claim 85 , wherein the antibody or antigen-binding fragment thereof is administered in multiple dosages. 
     
     
         94 . The method of  claim 85 , wherein the antibody or antigen-binding fragment thereof is administered as a sustained release composition. 
     
     
         95 . The method of  claim 85 , whereby deposition of AIAPP fibril aggregates is inhibited. 
     
     
         96 . The method of  claim 85 , whereby AIAPP fibril aggregates are cleared. 
     
     
         97 . The method of  claim 85 , whereby progression of the amyloid disease is delayed. 
     
     
         98 . A method of reducing risk or delaying onset of an amyloid disease in a patient at risk of having the amyloid disease, which disease is characterized by the presence of AIAPP fibrils, comprising administering to the patient an effective dosage of an antibody or fragment that specifically binds to AIAPP to thereby effect prophylaxis of the amyloid disease. 
     
     
         99 . The method of  claim 98 , wherein the islet amyloid polypeptide (AIAPP) fibrils are in amyloid deposits in pancreatic islet cells. 
     
     
         100 . The method of  claim 98 , wherein the amyloid disease is diabetes type II or insulinoma. 
     
     
         101 . The method of  claim 98 , wherein the antibody or antigen-binding fragment thereof binds to an aggregated amyloid fibril component with an affinity of greater than or equal to 10 6  M −1 . 
     
     
         102 . The method of  claim 98 , wherein the antibody or antigen-binding fragment thereof binds to a disaggregated amyloid fibril component with an affinity of less than 10 6  M −1 . 
     
     
         103 . The method of  claim 98 , wherein the antibody or antigen-binding fragment thereof binds to a precursor of an amyloid fibril component with an affinity of less than 10 6  M −1 . 
     
     
         104 . The method of  claim 98 , wherein the antibody is a human, chimeric, or humanized antibody. 
     
     
         105 . The method of  claim 104 , wherein the isotype of the antibody is human IgG1. 
     
     
         106 . The method of  claim 98 , wherein the antibody or antigen-binding fragment thereof is administered in multiple dosages. 
     
     
         107 . The method of claim  985 , wherein the antibody or antigen-binding fragment thereof is administered as a sustained release composition. 
     
     
         108 . The method of  claim 98 , whereby deposition of AIAPP fibril aggregates is inhibited. 
     
     
         109 . The method of  claim 98 , whereby AIAPP fibril aggregates are cleared.