Method for treating amyloid disease

Abstract

Disclosed herein are methods for treating amyloid disease in humans by clearing amyloid peptides from one or more bodily fluids such as, e.g., blood, of a patient. In particular, the methods are based on the administration capable of binding to amyloid-beta (Aβ) or on dialysis of blood or plasma exchange in order to remove Aβ peptides from the blood circulation, and/or brain or other affected organs.

1 . A method of treating a patient suffering from an amyloid disease comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound which binds to free amyloid-beta in a body fluid of the patient.  
     
     
         2 . The method of  claim 1 , wherein a binding complex is formed between the compound and Aβ.  
     
     
         3 . The method of  claim 1 , wherein the body fluid is blood.  
     
     
         4 . The method of  claim 1 , wherein the complex is excreted from the patient.  
     
     
         5 . The method of  claim 1 , wherein the amyloid disease is Alzheimer's disease.  
     
     
         6 . The method of  claim 1 , wherein the compound is administered systemically.  
     
     
         7 . The method of  claim 6 , wherein between about 1 mg and about 100 mg of the compound is administered per kg body weight of the patient and per day.  
     
     
         8 . The method of  claim 1 , wherein the compound is selected from apolipoprotein E, apolipoprotein J, serum amyloid P component, RNA aptamers directed against amyloid beta, α1-antichymotrypsin, a proteoglycan, a ganglioside, vimentin, vitronectin, albumin, transthyretin, an amyloid-beta-binding fragment thereof, and combinations thereof.  
     
     
         9 . The method of  claim 8 , wherein the apolipoprotein E is selected from apolipoprotein E2, apolipoprotein E3 or apolipoprotein E4.  
     
     
         10 . The method of  claim 8 , wherein said compound or fragment thereof is a mimetic of said compound or fragments thereof.  
     
     
         11 . The method of  claim 8 , wherein the proteoglycan is a heparan sulfate proteoglycan.  
     
     
         12 . The method of  claim 8 , wherein the ganglioside is selected from monosiologanglioside GM1, monosiologanglioside GM2, monosiologanglioside GM3, disialoganghoside GD1a, disialoganglioside GD1b, trisialoganglioside GT1b, and a mixture thereof.  
     
     
         13 . The method of  claim 1 , wherein the compound is an antibody or antibody fragment which binds to amyloid-beta.  
     
     
         14 . The method of  claim 1 , wherein the blood-brain-barrier is permeabilized prior to administration of the compound.  
     
     
         15 . The method of  claim 14 , wherein the blood-brain-barrier is permeabilized by administering insulin growth factor I (IGF-I).  
     
     
         16 . A method of treating an amyloid disease in a patient in need of such treatment comprising filtering the blood of the patient through a filter, membrane or column, thereby removing circulating amyloid-beta from the patient.  
     
     
         17 . The method of  claim 16 , wherein the filtered blood is returned to said patient.  
     
     
         18 . The method of  claim 16 , wherein the amyloid disease is Alzheimer's disease.  
     
     
         19 . The method of  claim 16 , wherein the membrane or filter has a cut-off weight of about 20 kD.  
     
     
         20 . The method of  claim 16 , wherein the membrane, filter or column comprises a compound which is bound or conjugated to the membrane, filter, or column and which binds to amyloid-beta.  
     
     
         21 . The method of  claim 20 , wherein the compound is selected from apolipoprotein E, apolipoprotein J, serum amyloid P component, a RNA aptamer directed against Aβ, α1-antichymotrypsin, a proteoglycan, a ganglioside, vimentin, vitronectin, albumin, transthyretin, amyloid-beta-binding fragments thereof, and combinations thereof.  
     
     
         22 . The method of  claim 21 , wherein the apolipoprotein E is selected from apolipoprotein E2, apolipoprotein E3 and apolipoprotein E4.  
     
     
         23 . The method of  claim 21 , wherein said compound or fragment thereof is a mimetic of said compound or fragments thereof.  
     
     
         24 . The method of  claim 21 , wherein the proteoglycan is a heparan sulfate proteoglycan.  
     
     
         25 . The method of  claim 21  wherein the ganglioside is selected from monosiologanglioside GM1, monosiologanglioside GM2, monosiologanglioside GM3, disialoganglioside GD1a, disialoganglioside GD1b, trisialoganglioside GT1b, and combinations thereof.  
     
     
         26 . The method of  claim 20 , wherein the compound is an antibody or antibody fragment which binds to amyloid-beta.  
     
     
         27 . The method according to  claim 16  wherein the method of filtering the blood of said patient is selected from hemodialysis, plasma perfusion and hemofiltration.