Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the 
gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule 
pharmacological chaperones have been shown to increase protein stability and 
cellular levels for mutant lysosomal enzymes and have emerged as a new 
therapeutic strategy for the treatment of LSDs. In this study, we characterized 
the pharmacological chaperone 1-deoxynojirimycin (DNJ) on 76 different mutant 
forms of GAA identified in Pompe disease. DNJ significantly increased enzyme 
activity and protein levels for 16 different GAA mutants in patient-derived 
fibroblasts and in transiently transfected COS-7 cells. Additionally, DNJ 
increased the processing of these GAA mutants to their mature lysosomal forms, 
suggesting facilitated trafficking through the secretory pathway. 
Immunofluorescence microscopy studies showed increased colocalization of GAA 
with the lysosomal marker LAMP2 after incubation with DNJ, confirming increased 
lysosomal trafficking. Lastly, a GAA structural model was constructed based on 
the related eukaryotic glucosidase maltase-glucoamylase. The mutated residues 
identified in responsive forms of GAA are located throughout most of the 
structural domains, with half of these residues located in two short regions 
within the catalytic domain. Taken together, these data support further 
evaluation of DNJ as a potential treatment for Pompe disease in patients that 
express responsive forms of GAA.