Screening molecules with anti-prion activity: kits, methods and screened molecules

Abstract

The invention concerns screening molecules with anti-prion activity. More particularly, it concerns kits for screening molecules with anti-prion activity characterized in that they comprise in combination a [PSI+], phenotype yeast, an antibiogram and an agent for purifying prions at sub-efficient doses, said yeast including the ade1-14 allele of the ADE1 gene and an inactivated ERG6 gene, the screening methods, and a family of molecules with anti-prion activity isolated by the inventive screen. The invention is applicable to anti-prion agents for producing medicines in particular for treating neurodegenerative diseases involving protein aggregates.

1 . A method for treating an animal or a human patient having a neurodegenerative disease responsive to treatment with an anti-prion agent, the method comprising administering to said animal or said human patient a pharmaceutical composition comprising:
 a therapeutically effective quantity of at least one compound of formula (II)   
       
         
           
           
               
               
           
         
         
           wherein R′ represents an NH 2 , or 
           NH—CH(CH 3 )—(CH 2 ) 3 —N(CH 2 —CH 3 ) 2  group, 
           X represents F, Cl, or CF 3 , 
           p and n, identical or different, are equal to 0, 1 or 2, 
         
         in combination with at least one pharmaceutically acceptable vehicle. 
       
     
     
         2 . The method of  claim 1 , wherein the neurodegenerative disease is selected from the group consisting of spongiform encephalopathies, Alzheimer's disease, Parkinson's disease and Huntington's disease. 
     
     
         3 . A method for treating an animal or a human patient having a neurodegenerative disease responsive to treatment with an anti-prion agent, the method comprising administering to said animal or said human patient a pharmaceutical composition comprising:
 a therapeutically effective quantity of at least one compound of formula (II)   
       
         
           
           
               
               
           
         
         
           wherein R′ represents NH 2 , 
           X represents F, Cl, or CF 3 , 
           p and n, identical or different, are equal to 0, 1 or 2 
         
         in combination with at least one pharmaceutically acceptable vehicle. 
       
     
     
         4 . The method of  claim 3 , wherein the neurodegenerative disease is selected from the group consisting of spongiform encephalopathies, Alzheimer's disease, Parkinson's disease and Huntington's disease. 
     
     
         5 . A method of treatment of an animal or human patient having a neurodegenerative disease, the method comprising administering to said animal or said human patient a therapeutically effective dose of a pharmaceutical composition comprising:
 a therapeutically effective quantity of at least one compound of formula (II)   
       
         
           
           
               
               
           
         
         
           wherein R′ represents an NH 2 , or 
           NH—CH(CH 3 )—(CH 2 ) 3 —N(CH 2 —CH 3 ) 2  group, 
           X represents F, Cl, or CF 3 , 
           p and n, identical or different, are equal to 0, 1 or 2, 
         
         in combination with at least one pharmaceutically acceptable vehicle, 
         for the treatment of said neurodegenerative disease. 
       
     
     
         6 . The method of  claim 5 , wherein the neurodegenerative disease is selected from the group consisting of spongiform encephalopathies, Alzheimer's disease, Parkinson's disease and Huntington's disease. 
     
     
         7 . A method of treatment of an animal or human patient having a neurodegenerative disease, the method comprising administering to said animal or said human patient a therapeutically effective dose of a pharmaceutical composition comprising:
 a therapeutically effective quantity of at least one compound of formula (II)   
       
         
           
           
               
               
           
         
         
           wherein R′ represents NH 2 , 
           X represents F, Cl, or CF 3 , 
           p and n, identical or different, are equal to 0, 1 or 2, 
         
         in combination with at least one pharmaceutically acceptable vehicle. 
       
     
     
         8 . The method of  claim 7 , wherein the neurodegenerative disease is selected from the group consisting of spongiform encephalopathies, Alzheimer's disease, Parkinson's disease and Huntington's disease. 
     
     
         9 . A method for treating an animal or a human patient having a neurodegenerative disease responsive to treatment with an anti-prion agent, the method comprising administering to said animal or said human patient a pharmaceutical composition comprising:
 a therapeutically effective quantity of at least one compound of formula (II)   
       
         
           
           
               
               
           
         
         
           wherein R′ is —NH—(CH 2 ) 3 —N(CH 3 ) 2 , 
           X is F, Cl, or CF 3 , and 
           p and n, identical or different, are equal to 1 or 2, 
         
         in combination with at least one pharmaceutically acceptable vehicle. 
       
     
     
         10 . The method of  claim 9 , wherein the neurodegenerative disease is selected from the group consisting of spongiform encephalopathies, Alzheimer's disease, Parkinson's disease and Huntington's disease. 
     
     
         11 . A method for treating an animal or a human patient having a neurodegenerative disease comprising administering to said animal or said human patient a therapeutically effective dose of a pharmaceutical composition of comprising:
 a therapeutically effective quantity of at least one compound of formula (II)   
       
         
           
           
               
               
           
         
         
           wherein R′ is —NH—(CH 2 ) 3 —N(CH 3 ) 2 , 
           X is F, Cl, or CF 3 , and 
           p and n, identical or different, are equal to 1 or 2, 
         
         in combination with at least one pharmaceutically acceptable vehicle. 
       
     
     
         12 . The method of  claim 11 , wherein the neurodegenerative disease is selected from the group consisting of spongiform encephalopathies, Alzheimer's disease, Parkinson's disease and Huntington's disease.