Therapy and diagnosis of conditions related to telomere length and/or telomerase activity

Abstract

Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity and means are shown for slowing the loss of telomeric repeats in aging cells.

1 . A method of inhibiting proliferation of mammalian cells which have telomerase activity, the method comprising: 
 administering an effective amount of a non-polynucleotide inhibitor of telomerase, other than AZT, thereby inhibiting telomerase activity in said cells.    
     
     
         2 . The method of  claim 1 , wherein said non-polynucleotide inhibitor reduces primer extension in a telomerase activity assay.  
     
     
         3 . The method of  claim 1 , wherein said cells are immortalized cells.  
     
     
         4 . The method of  claim 3 , wherein said cells are cancer cells.  
     
     
         5 . The method of  claim 4 , wherein said cells are leukemic cells.  
     
     
         6 . The method of  claim 4 , wherein said cells are non-leukemic cells.  
     
     
         7 . The method of  claim 6 , wherein said cells are solid tumor cells.  
     
     
         8 . The method of  claim 1 , wherein said cells are mammalian cells.  
     
     
         9 . The method of  claim 8 , wherein said cells are human cells, and said telomerase is human telomerase.  
     
     
         10 . The method of  claim 4 , wherein said cells are human cells, and said telomerase is human telomerase.  
     
     
         11 . The method of  claim 1 , wherein said non-polynucleotide inhibitor is a nucleoside analog.  
     
     
         12 . The method of  claim 11 , wherein said nucleoside analog is dideoxyguanosine.  
     
     
         13 . The method of  claim 1 , wherein said non-polynucleotide inhibitor is added to cells in culture.  
     
     
         14 . A pharmaceutical composition comprising a pharmaceutically acceptable buffer and an amount of a non-polynucleotide inhibitor of a mammalian telomerase, other than AZT, effective to inhibit telomerase-mediated extension of telomeres of mammalian cells which have telomerase, wherein said non-polynucleotide inhibitor reduces primer extension in a telomerase activity assay.  
     
     
         15 . The composition of  claim 14 , wherein said inhibitor is effective to inhibit telomerase-mediated extension of telomeres of mammalian solid tumor cells which have telomerase.  
     
     
         16 . The composition of  claim 14 , wherein said non-polynucleotide inhibitor is a nucleoside analog.  
     
     
         17 . The composition of  claim 16 , wherein said nucleoside analog is dideoxyguanosine.