Figure 1.

Depiction of rhGAA ERT distribution from the systemic circulation to the interstitial space surrounding muscle fibers. High resultant plasma concentrations of rhGAA (blue circles) can be attained post-intravenous administration but only a very small fraction reaches skeletal muscle. Substantial clearance of rhGAA from the circulation by non-muscle tissues and cells including liver, spleen, fibroblasts, etc. and an inefficient transcytosis process are believed to cause very poor distribution of rhGAA ERT to the interstitia. Receptor-mediated endocytosis is required for efficient cellular uptake of exogenous rhGAA in skeletal muscles (Van der Ploeg et al. 1988; Zhu et al. 2009; Xu et al. 2019). rhGAA, recombinant human acid alpha-glucosidase; ERT, enzyme replacement therapy.