Enzymatic replacement therapy and antisense therapy for pompe disease

Abstract

The present invention is direct to the treatment of Pompe disease by administration of an enzyme or nucleic acid encoding for said enzyme suitable for Enzyme Replacement Therapy for Pompe disease in combination with the administration of an antisense oligomeric compound that modulates the splicing of acid alpha-glucosidase (GAA) gene.

1 - 35 . (canceled) 
     
     
         36 . Antisense oligomeric compound comprising a sequence selected from the group consisting of SEQ ID NO: 1590-1594 and sequences having at least 80% identity thereof. 
     
     
         37 - 49 . (canceled) 
     
     
         50 . Antisense oligomeric compound as claimed in  claim 36 , wherein at least one of the nucleotides is modified. 
     
     
         51 . Antisense oligomeric compound as claimed in  claim 50 , wherein the oligomeric compound is uniformly modified. 
     
     
         52 . Antisense oligomeric compound as claimed in  claim 36 , wherein the sugar of one or more nucleotides is modified. 
     
     
         53 . Antisense oligomeric compound as claimed in  claim 52 , wherein the sugar modification is 2′-O-methyl or 2′-O-methoxyethyl. 
     
     
         54 . Antisense oligomeric compound as claimed in  claim 36 , wherein the base of one or more nucleotides is modified. 
     
     
         55 . Antisense oligomeric compound as claimed in  claim 36 , wherein the backbone of the oligomeric compound is modified. 
     
     
         56 . Antisense oligomeric compound as claimed in  claim 36 , wherein the oligomeric compound is morpholino phosphorothioate, or morpholino phosphorodiamidate, or tricyclo DNA. 
     
     
         57 . Method of modulating splicing of GAA pre-mRNA in a cell comprising contacting the cell with an antisense oligomeric compound as claimed in  claim 36 . 
     
     
         58 . Method for treating Pompe disease in a patient comprising administering to the patient an effective amount of an antisense oligomeric compound according to  claim 36 . 
     
     
         59 . Method to restore the function of GAA in a cell comprising the administration of the antisense oligomeric compound according to  claim 36 . 
     
     
         60 . Method of correcting abnormal gene expression in a cell of a subject, the method comprising administering to the subject an antisense oligomeric compound according to  claim 36 . 
     
     
         61 . Method of  claim 60 , wherein the cell is a muscular cell. 
     
     
         62 . Method according to  claim 57  wherein the cell comprises at least one mutation selected from the group c.-32-13T>G, c.-32-3C>G, c.547-6, c.1071, c.1254, and c.1552-30. 
     
     
         63 . Method according to  claim 58  wherein the patient comprises at least one mutation selected from the group c.-32-13T>G, c.-32-3C>G, c.547-6, c.1071, c.1254, and c.1552-30. 
     
     
         64 . Method according to  claim 59  wherein the cell comprises at least one mutation selected from the group c.-32-13T>G, c.-32-3C>G, c.547-6, c.1071, c.1254, and c.1552-30. 
     
     
         65 . Method according to  claim 60  wherein the cell comprises at least one mutation selected from the group c.-32-13T>G, c.-32-3C>G, c.547-6, c.1071, c.1254, and c.1552-30. 
     
     
         66 . Method according to  claim 58  wherein exon inclusion is accomplished. 
     
     
         67 . Method according to  claim 66 , wherein inclusion of exon 2 is accomplished. 
     
     
         68 . A pharmaceutical composition comprising at least one antisense oligomeric compound according to claim  1 . 
     
     
         69 . A pharmaceutical composition according to  claim 68  wherein said composition further comprises a pharmaceutical acceptable excipient and/or a cell delivery agent.