Prevention and treatment of amyloidogenic disease

Abstract

The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of Aβ and antibodies binding to the same.

What is claimed is:  
     
         1 . A method of therapeutically treating Alzheimer's disease comprising administering to the patient an effective dosage of a pharmaceutical composition comprising a humanized or chimeric antibody that specifically binds to an epitope within Aβ3-6, thereby treating Alzheimer's disease.  
     
     
         2 . The method of  claim 1 , wherein the patient is human.  
     
     
         3 . The method of  claim 1 , wherein after administration the antibody binds to an amyloid deposit in the patient and induces a clearing response against the amyloid deposit.  
     
     
         4 . The method of  claim 3 , wherein the clearing response is an Fc receptor mediated phagocytosis response.  
     
     
         5 . The method of  claim 4 , further comprising monitoring the clearing response.  
     
     
         6 . The method of  claim 1 , wherein the patient is asymptomatic.  
     
     
         7 . The method of  claim 1 , wherein the patient is under 50.  
     
     
         8 . The method of  claim 1 , wherein the patient has inherited risk factors indicating susceptibility to Alzheimer's disease.  
     
     
         9 . The method of  claim 1 , wherein the patient has no known risk factors for Alzheimer's disease.  
     
     
         10 . The method of  claim 1 , wherein the antibody is a polyclonal antibody.  
     
     
         11 . The method of  claim 1 , wherein the antibody is a monoclonal antibody.  
     
     
         12 . The method of  claim 1 , further comprising administering an effective dosage of at least one other antibody that binds to a different epitope of Aβ.  
     
     
         13 . The method of  claim 1 , wherein the antibody comprises two copies of the same pair of light and heavy chains.  
     
     
         14 . The method of  claim 1 , wherein the dosage of antibody is at least 1 mg/kg body weight of the patient.  
     
     
         15 . The method of  claim 1 , wherein the dosage of antibody is at least 10 mg/kg body weight of the patient.  
     
     
         16 . The method of  claim 1 , wherein the antibody is administered with a carrier.  
     
     
         17 . The method of  claim 1 , wherein the antibody specifically binds to Aβpeptide without binding to full-length amyloid precursor protein (APP).  
     
     
         18 . The method of  claim 1 , wherein the antibody is administered intraperitoneally, orally, subcutaneously, intranasally, intramuscularly, topically, or intravenously.  
     
     
         19 . The method of  claim 1 , further comprising monitoring the patient for level of administered antibody in the blood of the patient.  
     
     
         20 . The method of  claim 1 , wherein a single dosage of the antibody is administered on multiple occasions.  
     
     
         21 . The method of  claim 20 , wherein the single dosage is administered once every week, once per every two weeks, once a month, once every 3 to 6 months, or yearly.  
     
     
         22 . The method of  claim 20 , wherein the occasions occur over a period of at least six months.  
     
     
         23 . The method of  claim 21 , wherein the occasions occur over a period of at least six months.  
     
     
         24 . A method of prophylaxis of Alzheimer's disease comprising administering to the patient an effective dosage of a pharmaceutical composition comprising a humanized or chimeric antibody that specifically binds to an epitope within Aβ3-6, thereby effecting prophylaxis.  
     
     
         25 . The method of  claim 24 , wherein the patient is human.  
     
     
         26 . The method of  claim 24 , wherein after administration the antibody binds to an amyloid deposit in the patient and induces a clearing response against the amyloid deposit.  
     
     
         27 . The method of  claim 26 , wherein the clearing response is an Fc receptor mediated phagocytosis response.  
     
     
         28 . The method of  claim 27 , further comprising monitoring the clearing response.  
     
     
         29 . The method of  claim 24 , wherein the patient is asymptomatic.  
     
     
         30 . The method of  claim 24 , wherein the patient is under 50.  
     
     
         31 . The method of  claim 24 , wherein the patient has inherited risk factors indicating susceptibility to Alzheimer's disease.  
     
     
         32 . The method of  claim 24 , wherein the patient has no known risk factors for Alzheimer's disease.  
     
     
         33 . The method of  claim 24 , wherein the antibody is a polyclonal antibody.  
     
     
         34 . The method of  claim 24 , wherein the antibody is a monoclonal antibody.  
     
     
         35 . The method of  claim 24 , further comprising administering an effective dosage of at least one other antibody that binds to a different epitope of Aβ.  
     
     
         36 . The method of  claim 24 , wherein the antibody comprises two copies of the same pair of light and heavy chains.  
     
     
         37 . The method of  claim 24 , wherein the dosage of antibody is at least 1 mg/kg body weight of the patient.  
     
     
         38 . The method of  claim 24 , wherein the dosage of antibody is at least 10 mg/kg body weight of the patient.  
     
     
         39 . The method of  claim 24 , wherein the antibody is administered with a carrier.  
     
     
         40 . The method of  claim 24 , wherein the antibody specifically binds to Aβ peptide without binding to full-length amyloid precursor protein (APP).  
     
     
         41 . The method of  claim 24 , wherein the antibody is administered intraperitoneally, orally, subcutaneously, intranasally, intramuscularly, topically, or intravenously.  
     
     
         42 . The method of  claim 24 , further comprising monitoring the patient for level of administered antibody in the blood of the patient.  
     
     
         43 . The method of  claim 24 , wherein a single dosage of the antibody is administered on multiple occasions.  
     
     
         44 . The method of  claim 43 , wherein the single dosage is administered once every week, once per every two weeks, once a month, once every 3 to 6 months, or yearly.  
     
     
         45 . The method of  claim 43 , wherein the occasions occur over a period of at least six months.  
     
     
         46 . The method of  claim 44 , wherein the occasions occur over a period of at least six months.