Table 2.

Current treatment strategies in place or being considered in Pompe disease

• Enzyme replenishment through enzyme replacement therapy (ERT) and enzyme enhancement  ○ BisM6P enrichment   ▪ Through chemical conjugation of synthetic linkers   ▪ Through clonal selection of rhGAA with CHO-cell derived M6P and bis-M6P moieties  ○ IGF-2 receptor related GILT-tagging  ○ Monoclonal antibody driven entry into muscle using CD63 and ITGA7 • Minimizing rhGAA inactivation in circulation with small molecule enzyme stabilizer • Delivery of full length gene through viral delivery for production of endogenous GAA  ○ Liver approach  ○ Muscle approach  ○ Intrathecal or intraventricular approach • Ex-vivo genetic modification of hematopoietic (CD34 +) stem cells (HSCs) through a lentiviral approach to express GILT-tagged GAA enzyme • Antisense approach to improve the IVS splicing variant • Substrate Reduction therapy (SRT)  ○ Small molecule approach  ○ Antisense approach