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Molecular Approaches for the Treatment of Pompe Disease

  • Anita Sofia Bellotti
  • Luca Andreoli
  • Dario Ronchi
  • Nereo Bresolin
  • Giacomo P. Comi
  • Stefania CortiEmail author
Article
First Online:

Abstract

Glycogen storage disease type II (GSDII, Pompe disease) is a rare metabolic disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme localized within lysosomes that is solely responsible for glycogen degradation in this compartment. The manifestations of GSDII are heterogeneous but are classified as early or late onset. The natural course of early-onset Pompe disease (EOPD) is severe and rapidly fatal if left untreated. Currently, one therapeutic approach, namely, enzyme replacement therapy, is available, but advances in molecular medicine approaches hold promise for even more effective therapeutic strategies. These approaches, which we review here, comprise splicing modification by antisense oligonucleotides, chaperone therapy, stop codon readthrough therapy, and the use of viral vectors to introduce wild-type genes. Considering the high rate at which innovations are translated from bench to bedside, it is reasonable to expect substantial improvements in the treatment of this illness in the foreseeable future.

Keywords

GSDII Pompe disease Alpha-glucosidase (GAA) Therapy Gene therapy Molecular therapy Antisense oligonucleotides 
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Notes

Funding Information

We thank the Associazione del Centro Dino Ferrari for their support. The work was partially funded by the Ministry of Health (to N.B., G.P.C., and S.C.). The figure was modified from images from Servier Medical Art, licensed under a Creative Common Attribution 3.0 Generic License. http://smart.servier.com/.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. 1.Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT)University of MilanMilanItaly
  2. 2.Neurology UnitFoundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Neuromuscular and Rare Diseases UnitFoundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly

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