Thursday, December 13, 2012
Researchers from Oxyrane U.K. Ltd. and BioMarin Pharmaceutical Inc. have separately published two new
strategies for delivering Pompe's disease enzyme replacement therapy.
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.
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).
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.