Combination enzyme replacement, gene therapy and small molecule therapy for lysosomal storage diseases

Abstract

This invention provides various combinations of enzyme replacement therapy, gene therapy, and small molecule therapy for the treatment of lysosomal storage diseases.

What is claimed is:  
     
         1 . A method of combination therapy for treatment of a subject diagnosed as having Fabry disease comprising administering a therapeutically effective amount of a combination therapy selected from two or more of an enzyme replacement therapy, gene therapy, and a small molecule therapy.  
     
     
         2 . The method according to  claim 1  wherein the combination therapy comprises alternating between administration of an enzyme replacement therapy and a small molecule therapy.  
     
     
         3 . The method according to  claim 1  wherein the combination therapy comprises simultaneously administering an enzyme replacement therapy and a small molecule therapy.  
     
     
         4 . The method according to  claim 1  wherein the combination therapy comprises gene therapy and a therapy selected from the group consisting of enzyme replacement therapy and small molecule therapy.  
     
     
         5 . The method according to  claim 1  wherein the combination therapy produces a diminution in globotriaosylceramide.  
     
     
         6 . The method according to  claim 1  wherein the enzyme replacement therapy provides an effective amount of α-galactosidase A.  
     
     
         7 . The method according to  claim 1  wherein the small molecule therapy comprises administering to the subject an effective amount of deoxynojirimycin or a deoxynojirimycin derivative.  
     
     
         8 . The method according to  claim 7 , wherein the deoxynojirimycin derivative is N-butyldeoxynojirimycin (NB-DNJ) or N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (AMP-DNJ).  
     
     
         9 . The method according to  claim 1 , wherein the small molecule therapy comprises administering to the subject an effective amount of a D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4) derivative.  
     
     
         10 . The method according to  claim 9 , wherein the P4 derivative is D-threo-1-(3′,4′-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (D-t-et-P4).  
     
     
         11 . The method according to  1 , wherein Fabry disease has at least one central nervous system manifestation and the small molecule therapy comprises AMP-DNJ.