Combination 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.

1 - 11 . (canceled) 
     
     
         12 . A method of treatment for a subject diagnosed with a lysosomal storage disease, comprising administering a therapeutically effective amount of a combination therapy, wherein the combination therapy comprises gene therapy and at least one of an enzyme replacement therapy and a small molecule therapy. 
     
     
         13 . The method of  claim 12 , wherein administering at least one of enzyme replacement therapy and small molecule therapy comprises alternating between administration of an enzyme replacement therapy and a small molecule therapy. 
     
     
         14 . The method of  claim 12 , wherein administering at least one of enzyme replacement therapy and small molecule therapy comprises simultaneously administering an enzyme replacement therapy and a small molecule therapy. 
     
     
         15 . The method of  claim 12 , wherein the lysosomal storage disease is Gaucher's disease, Fabry disease, Pompe disease, Niemann-Pick disease, or mucopolysaccharidosis (MPS). 
     
     
         16 . The method of  claim 15 , wherein the MPS is MPS I, MPS II, MPS IV, or MPS VI. 
     
     
         17 . The method of  claim 12 , wherein the gene therapy provides a therapeutically effective amount of a lysosomal hydrolase. 
     
     
         18 . The method of  claim 12 , wherein the gene therapy comprises administering to the subject an adeno-associated virus (AAV) vector encoding a lysosomal hydrolase. 
     
     
         19 . The method of  claim 12 , wherein the combination therapy comprises gene therapy and enzyme replacement therapy. 
     
     
         20 . The method of  claim 19 , wherein the enzyme replacement therapy comprises administering a therapeutically effective amount of a lysosomal hydrolase. 
     
     
         21 . The method of  claim 12 , wherein the combination therapy comprises gene therapy and small molecule therapy. 
     
     
         22 . The method of  claim 21 , wherein the small molecule therapy comprises administering to the subject a therapeutically effective amount of a small molecule chosen from D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4) and a P4 derivative. 
     
     
         23 . The method of  claim 22 , wherein the P4 derivative is D-threo-1-(3′,4′-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (D-t-et-P4). 
     
     
         24 . The method of  claim 21 , wherein the small molecule therapy comprises administering to the subject a therapeutically effective amount of a small molecule chosen from deoxynojirimycin (DNJ) and a DNJ derivative. 
     
     
         25 . The method of  claim 24 , wherein the DNJ derivative is N-butyldeoxynojirimycin (NB-DNJ) or N-(5-adamantane-1-yl-methoxy)pentyl-deoxynojirimycin (AMP-DNJ). 
     
     
         26 . A method of treatment for a subject diagnosed as having a lysosomal storage disease, comprising administering a therapeutically effective amount of a combination therapy selected from two or more of gene therapy, an enzyme replacement therapy, and a small molecule therapy. 
     
     
         27 . The method of  claim 26 , wherein the combination therapy comprises administering to the subject an adeno-associated virus (AAV) vector encoding a lysosomal hydrolase. 
     
     
         28 . The method of  claim 26 , wherein the combination therapy comprises administering a therapeutically effective amount of a lysosomal hydrolase enzyme replacement therapy. 
     
     
         29 . The method of  claim 26 , wherein the combination therapy comprises administering to the subject a therapeutically effective amount of a small molecule chosen from D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4) and a P4 derivative. 
     
     
         30 . The method of  claim 29 , wherein the P4 derivative is D-threo-1-(3′,4′-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (D-t-et-P4). 
     
     
         31 . The method of  claim 26 , wherein the combination therapy comprises administering to the subject a therapeutically effective amount of a small molecule chosen from deoxynojirimycin (DNJ) and a DNJ derivative. 
     
     
         32 . The method of  claim 31 , wherein the DNJ derivative is N-butyldeoxynojirimycin (NB-DNJ) or N-(5-adamantane-1-yl-methoxy)pentyl-deoxynojirimycin (AMP-DNJ). 
     
     
         33 . The method of  claim 26 , wherein the lysosomal storage disease is Gaucher's disease, Fabry disease, Pompe disease, Niemann-Pick disease, or mucopolysaccharidosis (MPS). 
     
     
         34 . The method of  claim 33 , wherein the MPS is MPS I, MPS II, MPS IV, or MPS VI.