Methods for treating neurological disorders

Abstract

Disclosed herein are methods and compositions for treating, ameliorating, and/or preventing Alzheimer's disease in ApoE4-postitive patients using particular compounds and compositions thereof.

1 . A method of treating Alzheimer's disease in an ApoE4-positive patient comprising the steps of:
 (i) testing an Alzheimer's patient for an ApoE4 allele,   (ii) characterizing a patient having an ApoE4 allele as ApoE4-positive, and   (iii) administering to the ApoE4-positive patient, for a period of time, a compound of Formula I   
       
         
           
           
               
               
           
         
         wherein the period of time is at least 13 weeks; 
         wherein the ADAS-cog score is tested at the end of the period of time and is improved by at least about 1.5-fold, compared to administration of a placebo to the ApoE4-positive patient over the same period of time. 
       
     
     
         2 . The method of  claim 1  wherein the Alzheimer's patient is heterozygous for the ApoE4 allele. 
     
     
         3 . The method of  claim 1  wherein the Alzheimer's patient is homozygous for the ApoE4 allele. 
     
     
         4 . The method of  claim 1  wherein the period of time is at least 26 weeks and the improvements is at least about 2.20-fold. 
     
     
         5 . The method of  claim 1  wherein the period of time is at least 39 weeks and the improvements is at least about 3.0-fold. 
     
     
         6 . The method of  claim 1  wherein the period of time is at least 65 weeks and the improvements is at least about 4.5-fold. 
     
     
         7 . The method of  claim 1  wherein AA 1  and AA 2  are independently selected from alanine (Ala), cysteine (Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (Ile), lysine (Lys), leucine (Leu), methionine (Met), asparagine (Asn), proline (Pro), glutamine (Gln), arginine (Arg), serine (Ser), threonine (Thr), valine (Val), tryptophan (Trp), tyrosine (Tyr), β-alanine (β-ALA), and γ-aminobutyric acid (GABA). 
     
     
         8 . A method of treating Alzheimer's disease in an ApoE4-positive patient comprising the steps of:
 (i) testing an Alzheimer's patient for an ApoE4 allele,   (ii) characterizing a patient having an ApoE4 allele as ApoE4-positive, and   (iii) administering to the ApoE4-positive patient, for a period of time, a compound of Formula I   
       
         
           
           
               
               
           
         
         wherein the period of time is at least 13 weeks; 
         wherein the ADAS-cog score is tested at the end of the period of time and is improved by at least about 1.5-fold, compared to administration of a placebo to the ApoE4-positive patient over the same period of time. 
       
     
     
         9 . The method of  claim 8  wherein the Alzheimer's patient is heterozygous for the ApoE4 allele. 
     
     
         10 . The method of  claim 8  wherein the Alzheimer's patient is homozygous for the ApoE4 allele. 
     
     
         11 . The method of  claim 8  wherein the period of time is at least 26 weeks and the improvements is at least about 2.20-fold. 
     
     
         12 . The method of  claim 8  wherein the period of time is at least 39 weeks and the improvements is at least about 3.0-fold. 
     
     
         13 . The method of  claim 8  wherein the period of time is at least 65 weeks and the improvements is at least about 4.5-fold. 
     
     
         14 . The method of  claim 8  wherein AA 1  is selected from the group consisting of: alanine (Ala), cysteine (Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (Ile), lysine (Lys), leucine (Leu), methionine (Met), asparagine (Asn), proline (Pro), glutamine (Gln), arginine (Arg), serine (Ser), threonine (Thr), valine (Val), tryptophan (Trp), tyrosine (Tyr), β-alanine (β-ALA), and γ-aminobutyric acid (GABA). 
     
     
         15 . The method of  claim 14  wherein AA 1  is selected from the group consisting of: alanine (Ala), isoleucine (Ile), leucine (Leu), serine (Ser), and valine (Val). 
     
     
         16 . The method of  claim 15  wherein AA 1  is valine (Val). 
     
     
         17 . The method of  claim 8  wherein the compound is administered once-daily.