Prevention and treatment of amyloidogenic diseases

Abstract

Active immunotherapy methods for treating a human patient having an amyloid disease characterized by the presence of amyloid fibrils comprising islet amyloid polypeptide (IAPP).

1 - 57 . (canceled) 
     
     
         58 . A method of therapeutically treating a human patient having an amyloid disease characterized by the presence of amyloid fibrils comprising islet amyloid polypeptide (IAPP), the method comprising administering to the patient islet amyloid polypeptide (IAPP) or islet amyloid polypeptide precursor or a fragment thereof, which effects an immune response comprising antibodies against islet amyloid polypeptide (IAPP). 
     
     
         59 . The method of  claim 58 , wherein the amyloid fibrils are in amyloid deposits in pancreatic islet cells. 
     
     
         60 . The method of  claim 58 , wherein the amyloid disease is associated with diabetes type II or insulinoma. 
     
     
         61 . The method of  claim 58 , wherein the islet amyloid polypeptide (IAPP), islet amyloid polypeptide precursor, or a fragment thereof, 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 islet amyloid polypeptide (IAPP). 
     
     
         66 . The method of  claim 65 , wherein the immune response is characterized by a serum titer of the antibodies of at least 1:5000 with respect to islet amyloid polypeptide (IAPP). 
     
     
         67 . The method of  claim 58 , wherein the immune response is characterized by a serum titer of the antibodies against islet amyloid polypeptide (IAPP) or islet amyloid polypeptide precursor that is greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample. 
     
     
         68 . The method of  claim 58 , further comprising administering simultaneously or sequentially in either order an adjuvant that augments the immune response. 
     
     
         69 . The method of  claim 68 , wherein the adjuvant is QS21, monophosphoryl lipid, or alum. 
     
     
         70 . The method of  claim 58 , whereby deposition of the amyloid fibrils comprising islet amyloid polypeptide (IAPP) is inhibited. 
     
     
         71 . The method of  claim 58 , whereby the amyloid fibrils comprising islet amyloid polypeptide (IAPP) are cleared. 
     
     
         72 . The method of  claim 58 , whereby progression of the amyloid disease is delayed. 
     
     
         73 . A method of reducing risk or delaying onset of an amyloid disease in a human patient at risk of amyloid disease, which disease is characterized by the presence of islet amyloid polypeptide (IAPP) fibrils, comprising administering to the patient islet amyloid polypeptide (IAPP) or islet amyloid polypeptide precursor or a fragment thereof, which effects an immune response comprising antibodies against islet amyloid polypeptide (IAPP). 
     
     
         74 . The method of  claim 73 , wherein the amyloid fibrils are in amyloid deposits in pancreatic islet cells. 
     
     
         75 . The method of  claim 73 , wherein the amyloid disease is associated with diabetes type II or insulinoma. 
     
     
         76 . The method of  claim 73 , wherein the islet amyloid polypeptide (IAPP), islet amyloid polypeptide precursor, or a fragment thereof, is linked to a carrier molecule. 
     
     
         77 . The method of  claim 76 , wherein the carrier molecule is a T-cell epitope. 
     
     
         78 . The method of  claim 76 , wherein the carrier molecule is a tetanus toxoid epitope. 
     
     
         79 . The method of  claim 76 , wherein the carrier molecule is a diphtheria toxoid epitope. 
     
     
         80 . The method of  claim 73 , wherein the immune response is characterized by a serum titer of the antibodies of at least 1:1000 with respect to islet amyloid polypeptide (IAPP). 
     
     
         81 . The method of  claim 80 , wherein the immune response is characterized by a serum titer of the antibodies of at least 1:5000 with respect to islet amyloid polypeptide (IAPP). 
     
     
         82 . The method of  claim 73 , wherein the immune response is characterized by a serum titer of the antibodies against islet amyloid polypeptide (IAPP) or islet amyloid polypeptide precursor that is greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample. 
     
     
         83 . The method of  claim 73 , further comprising administering simultaneously or sequentially in either order an adjuvant that augments the immune response. 
     
     
         84 . The method of  claim 82 , wherein the adjuvant is QS21, monophosphoryl lipid, or alum. 
     
     
         85 . The method of  claim 73 , whereby deposition of the amyloid fibrils comprising islet amyloid polypeptide (IAPP) is inhibited. 
     
     
         86 . The method of  claim 73 , whereby the amyloid fibrils comprising islet amyloid polypeptide (IAPP) are cleared.