Enzyme replacement therapy for the treatment of Pompe disease

ABSTRACT

Introduction: Glycogenosis type II (GSDII or acid maltase deficiency) is a rare autosomal disorder caused by deficiency of alpha-glucosidase, a lysosomal enzyme that hydrolyzes glycogen to glucose.

Areas covered: Since 2006, both infantile (classic Pompe disease) and adult GSDII (late onset pompe disease or LOPD) patients have been treated with enzyme replacement therapy (ERT), and various double blind or observational studies including large cohorts of GSDII patients have recently demonstrated that ERT is effective in modifying the natural course of the disease. Most LOPD cases show an improvement in the first 20 months of treatment of about 50 m in six-minute walk test (6 MWT); vice versa, untreated patients do not show 6MWT improvement over time. Pathophysiologic aspects such as the role of autophagy in natural history and the response to ERT treatment are considered in this review.

Expert opinion: The opportunity of ERT treatment improved quality of life for GSDII patients. There has been an important impulse to research various aspects of the disease in relation to both the role of autophagy and the role of immune tolerance, leading to a deeper knowledge of clinical manifestations.

KEYWORDS:

• Acid alpha-glucosidase deficiency
• autophagy
• enzyme replacement therapy
• glycogenosis type II
• Pompe disease

Article highlights

• Enzyme replacement therapy is an effective treatment of classic infantile and late-onset Pompe patients.

• Increased survival and reversal of cardiomyopathy is observed in infantile Pompe disease.

• ERT positively affects muscle strength, pulmonary function and daily life activities in adult Pompe patients.

• In adult Pompe maximal ERT efficacy was observed in the first two years.

• Future prospects of al-glucosidase treatment include improved enzyme preparation as well as combination with other drugs.

This box summarizes key points contained in the article.

Declaration of interest

The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Additional information

Funding

Fondazione Telethon [GUP13013].