Acid-alpha glucosidase variants and uses thereof

Abstract

The present invention relates to variants of acid-alpha glucosidase and uses thereof. Said variants are sequence-optimized and/or are linked to a heterogenous signal peptide.

We claim: 
     
         1 . A functional chimeric acid alpha-glucosidase (GAA) polypeptide having acid alpha-glucosidase activity, comprising the signal peptide of the human alpha-1-antitrypsin protein fused to the functional GAA polypeptide having acid alpha-glucosidase activity, wherein the functional GAA polypeptide having acid alpha-glucosidase activity is encoded by a nucleotide sequence having at least 85% identity to SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         2 . A pharmaceutical composition, comprising, in a pharmaceutically acceptable carrier the chimeric GAA polypeptide according to  claim 1  or a nucleic acid encoding said chimeric GAA polypeptide. 
     
     
         3 . A method of treating a glycogen storage disease comprising the administration of a nucleic acid molecule encoding a functional chimeric GAA polypeptide, comprising the signal peptide of the human alpha-1-antitrypsin protein fused to a functional GAA polypeptide, wherein the functional GAA polypeptide is encoded by a nucleotide sequence having at least 85% identity to SEQ ID NO: 1 or SEQ ID NO: 2, a nucleic acid construct comprising said nucleic acid molecule or a chimeric GAA polypeptide encoded by said nucleic acid molecule to a subject having a glycogen storage disease. 
     
     
         4 . The method according to  claim 3 , wherein said glycogen storage disease is GSDI (von Gierke's disease), GSDII (Pompe disease), GSDIII (Cori disease), GSDIV, GSDV, GSDVI, GSDVII, or GSDVIII and lethal congenital glycogen storage disease of the heart.