Methods of reducing beta-amyloid polypeptides

Abstract

The invention features methods of reducing the level of a β-amyloid (Aβ) polypeptide using an Cimicifuga extract. The invention also features methods of producing an active fraction from an extract of Cimicifuga . The invention further features a composition containing an active fraction of a Cimicifuga extract and an article of manufacture containing such a composition.

1 . A method of preferentially reducing the level of a β-amyloid (Aβ) polypeptide in or secreted from a cell, wherein the Aβ is Aβ 40 or Aβ 42, or a mutant thereof said method comprising contacting said cell with an amount of a  Cimicifuga  extracts or of an active fraction thereof, effective for reducing the level of said Aβ polypeptide in or secreted from said cell and monitoring the level of said Aβ polypeptide in or secreted from said cell. 
   
   
       2 . The method of  claim 1 , wherein said  Cimicifuga  extract or active fraction thereof is from  C. racemosa.    
   
   
       3 . The method of  claim 2 , wherein said  C. racemosa  extract or active fraction thereof is obtained from the root or rhizome of a  C. racemosa  plant. 
   
   
       4 .- 7 . (canceled) 
   
   
       8 . The method of  claim 1 , wherein said cell is selected from the group consisting of H4 cells, M17 cells, 293 cells, Chinese hamster ovary (CHO) cells, primary fibroblasts, C6, primary neuronal, primary mixed brain cultures, Daoy, SK-N-SH, SK-N-AS and SK-N-FI. 
   
   
       9 . The method of  claim 1 , wherein said reduction in the level of said Aβ polypeptide is due to decreased production of said Aβ polypeptide or increased catabolism of said Aβ polypeptide. 
   
   
       10 . The method of  claim 1 , wherein said level of said Aβ polypeptide is reduced by at least 10% compared to the level of said Aβ polypeptide in or secreted from a corresponding cell not contacted with said extract or active fraction thereof. 
   
   
       11 . The method of  claim 1 , wherein said level of said Aβ polypeptide is reduced by at least 25% compared to the level of said Aβ polypeptide in or secreted from a corresponding cell not contacted with said extract or active fraction thereof. 
   
   
       12 . The method of  claim 1 , wherein said level of said Aβ polypeptide is reduced by at least 50% compared to the level of said Aβ polypeptide in or secreted from a corresponding cell not contacted with said extract or active fraction thereof. 
   
   
       13 . The method of  claim 1 , wherein said level of said Aβ polypeptide is reduced by at least 80% compared to the level of said Aβ polypeptide in or secreted from a corresponding cell not contacted with said extract or active fraction thereof. 
   
   
       14 .- 16 . (canceled) 
   
   
       17 . The method of  claim 1 , wherein said extract or active fraction thereof has no significant effect on the level of one or more of APP, CTF.alpha., CTF.beta., or sAPP.alpha. 
   
   
       18 . A method for reducing the level of an Aβ polypeptide in a mammal, wherein the Aβ is Aβ 40 or Aβ 42, or a mutant thereof said method comprising administering an amount of a  Cimicifuga  extract or an active fraction thereof to said mammal effective for reducing the level of said Aβ polypeptide. 
   
   
       19 . The method of  claim 18 , wherein said extract or active fraction thereof is administered to said mammal orally, intravenously, intracranially, intracerebrally, subcutaneously, intramuscularly, intranasally or intraperitoneally. 
   
   
       20 .- 23 . (canceled) 
   
   
       24 . A method of treating a mammal having Alzheimer's disease, or at risk to develop Alzheimer's disease, said method comprising administering an amount of a  Cimicifuga  extracts or an active fraction thereof, to said mammal and preferentially reducing the level of Aβ 40 or Aβ 42, or a mutant thereof. 
   
   
       25 .- 36 . (canceled) 
   
   
       37 . A composition comprising an active fraction of a  Cimicifuga  extract and a pharmaceutically acceptable carrier, wherein said active fraction reduces the level of an Aβ polypeptide upon contact with a cell producing said Aβ polypeptide, wherein said composition is formulated as a tablet or capsule for oral administration. 
   
   
       38 . The composition according to  claim 37 , wherein said active fraction preferentially reduces the level of Aβ 40 or Aβ 42, or a mutant thereof. 
   
   
       39 . The composition according to  claim 37 , wherein the tablet or capsule is formulated for controlled-release of the active fraction of a  Cimicifuga  extract. 
   
   
       40 . A method for identifying an active fraction of a  Cimicifuga  extract, comprising the steps of:
 providing one or more  Cimicifuga  extracts;   optionally providing one or more control compounds;   contacting the one or more  Cimicifuga  extracts and, optionally, the one or more control compounds, with a cell; and   measuring the level of an Aβ polypeptide produced by the cell.   
   
   
       41 . The method according to  claim 40 , wherein the level of Aβ 40 or Aβ 42, or a mutant thereof, is measured. 
   
   
       42 . The method according to  claim 40 , further comprising the step of comparing levels of an Aβ polypeptide resulting from different  Cimicifuga  extracts. 
   
   
       43 . The method according to  claim 40 , further comprising the steps of measuring the levels of one or more of APP, CTFα, CTFβ, or sAPPα.