Pompe Disease: New Developments in an Old Lysosomal Storage Disorder

Biomolecules. 2020 Sep 18;10(9):1339. doi: 10.3390/biom10091339.

PMID: 32962155

Naresh K Meena, Nina Raben

Summary: Enzyme replacement therapy (ERT) is the only disease-specific treatment available for Pompe disease patients. The success and limitations of ERT revealed new insights into the pathophysiology of the disease, leading the development of the next generation therapies, which have already progressed to the clinic.

Abstract

Background: Pompe disease, commonly known as glycogen storage disorder type II, is caused by a single enzyme, lysosomal acid alpha-glucosidase, being absent or deficient, resulting in severe cardiac and skeletal muscle myopathy due to progressive accumulation of glycogen. The revelation that acid alpha-glucosidase resides in the lysosome gave rise to the idea of lysosomal storage illnesses, with Pompe disease becoming the first of several monogenic disorders characterized by lysosomal enzyme activity decrease.

Conclusion: Enzyme replacement therapy (ERT), which aims to halt the natural course of the illness, is the only disease-specific treatment available for Pompe disease patients. The success and limitations of ERT revealed new insights into the pathophysiology of the disease, motivating scientists to develop the next generation of medicines, which have already progressed to the clinic.

Keywords: Pompe disease; autophagy; enzyme replacement therapy; gene therapy; lysosomal targeting; lysosome; muscle; satellite cells.