Figure 1. Next-generation Myozyme. Researchers from Oxyrane U.K. Ltd. and BioMarin Pharmaceutical Inc. have separately published two new strategies for delivering Pompe's disease enzyme replacement therapy.

Pompe's disease results from a lack of or deficiency in the enzyme acid a-glucosidase (GAA), which leads to pathological buildup of glycogen in the lysosomes of muscle cells. The only drugs approved for the disease are Myozyme and Lumizyme, enzyme replacement therapies marketed by Sanofi's Genzyme Corp. unit.

The new strategies each modify GAA to enhance its affinity for its receptor on muscle cells, potentially allowing for the use of lower doses than those for Myozyme. BioMarin attached the peptide insulin-like growth factor-2 (IGF-2) to GAA, creating a compound dubbed BMN-701 (IGF-2-GAA), whereas Oxyrane enriched the surface of GAA with the carbohydrate mannose-6-phosophate (M-6-P).

The modified forms of GAA bound their receptor, insulin-like growth factor 2 receptor (IGF2R; M6PR), on the surface of muscle cells [a]
and were internalized by receptor-mediated endocytosis [b]. In mice, GAA broke down glycogen deposits in the lysosome [c] and decreased muscle tissue pathology better than unmodified GAA or Myozyme.