Enzyme-Replacement Therapy for Pompe Disease

Pompe disease (α-glucosidase deficiency; also known as glycogen storage disease type II) is the first lysosomal storage disorder for which the biochemical basis was determined. Development of enzyme-replacement therapy for Pompe disease initially involved competing commercial interests and clinical trials using two different enzyme formulations, including one derived from transgenic rabbit’s milk. Further studies have since been conducted with the enzyme generated from transduction of Chinese hamster ovary cells. Therapeutic benefits have been observed in treated patients with either the infantile or late-onset form of Pompe disease; clinical subtypes with marked differences in clinical course and survival. Several factors, including disease duration and antibody formation, appear to influence clinical outcome of enzyme-replacement therapy. Recently, defects of autophagy have been demonstrated; these changes may represent a separate target for therapeutic intervention to optimize outcome. Meanwhile, issues that require further investigation include pathogenesis, ways to improve the means of targeting of recombinant enzyme to skeletal muscle, means to facilitate an early diagnosis and the benefit of early intervention, particularly for the late-onset forms of the disease. Moreover, other therapeutic strategies, such as the use of pharmacologic chaperone and gene therapy, are under investigation.