Aminoglycoside treatment for lysosomal storage diseases

Abstract

The present invention provides a method of treating lysosomal storage diseases such as Hurler syndrome and Batten disease in individuals in need of such treatment, comprising the step of administering to said individuals a therapeutically effective dose of an aminoglycoside. In addition, this method may further comprise treating the individual with enzyme replacement therapy. Furthermore, the present invention provides method of pharmacologically suppressing premature stop mutations in an individual with these lysosomal storage diseases, comprising the step of administering to said individual a pharmacologically effective dose of an aminoglycoside.

1 - 32 . (canceled)  
     
     
         33 . A method of treating a lysosomal storage disease in an individual in need of such treatment, comprising: 
 administering to said individual a therapeutically effective dose of an aminoglycoside in combination with one or more of an enzyme effective for enzyme replacement therapy, a polyionic compound or a gene therapy vector.    
     
     
         34 . The method of  claim 33 , wherein said lysosomal storage disease is Hurler syndrome.  
     
     
         35 . The method of  claim 34 , wherein said aminoglycoside suppresses a naturally occurring premature stop mutation.  
     
     
         36 . The method of  claim 35 , wherein said naturally occurring premature stop mutation is selected from the group consisting of IDUA-Q70X stop mutation and the IDUA-W402X stop mutation.  
     
     
         37 . The method of  claim 34 , wherein said enzyme effective for enzyme replacement therapy is recombinant alpha-L iduronidase.  
     
     
         38 . The method of  claim 37 , wherein said enzyme is ALDURAZYME®.  
     
     
         39 . The method of  claim 34 , wherein said gene therapy vector encodes alpha L-iduronidase.  
     
     
         40 . The method of  claim 33 , wherein said lysosomal storage disease is Batten disease.  
     
     
         41 . The method of  claim 40 , wherein said aminoglycoside suppresses a naturally occurring premature stop mutation.  
     
     
         42 . The method of  claim 40 , wherein said enzyme effective for enzyme replacement therapy is recombinant tripeptidyl-peptidase-1 (encoded by the human CLN2 gene).  
     
     
         43 . The method of  claim 40 , wherein said gene therapy vector encodes tripeptidyl-peptidase-1 (encoded by the human CLN2 gene).  
     
     
         44 . The method of  claim 33 , wherein said enzyme replacement therapy is performed either prior to said aminoglycoside treatment, concurrently with said aminoglycoside treatment or subsequent to said aminoglycoside treatment.  
     
     
         45 . The method of  claim 33 , wherein said aminoglycoside is selected from the group consisting of gentamicin, G418, hygromycin B, paromomycin, tobramycin, lividomycin A, amikacin, sisomycin and neomycin.  
     
     
         46 . The method of  claim 45 , wherein said gentamycin is administered in a dose of from about 1 mg/kg to about 500 mg/kg.  
     
     
         47 . The method of  claim 33 , wherein said poly-anionic compound is selected from the group consisting of poly L-aspartic acid and daptomycine.