Enzyme replacement therapy for late-onset Pompe disease

Area of Science:

• Biochemistry
• Genetics
• Clinical Medicine

Background:

• Pompe disease results from acid alpha-glucosidase (GAA) enzyme deficiency.
• Late-onset Pompe disease (LOPD) involves partial GAA deficiency.
• Enzyme replacement therapy (ERT) using alglucosidase alfa and avalglucosidase alfa are approved treatments.

Approach:

• Systematic review of randomized controlled trials (RCTs) for ERT in LOPD.
• Searched multiple databases and trial registries up to April 2022.
• Assessed trial eligibility, data extraction, risk of bias, and certainty of evidence (GRADE).

Key Points:

• Alglucosidase alfa likely improves 6-minute walk test (6MWT) distance and forced vital capacity (FVC) compared to placebo (moderate-certainty evidence).
• Avalglucosidase alfa likely improves 6MWT compared to alglucosidase alfa (moderate-certainty evidence).
• Cipaglucosidase alfa plus miglustat likely improves FVC compared to alglucosidase alfa plus placebo (moderate-certainty evidence).

Conclusions:

• ERTs demonstrate probable benefits in 6MWT and respiratory function for LOPD.
• Evidence for adjunct therapies (clenbuterol, albuterol) with ERT is limited.
• Longer RCTs and post-marketing registries are recommended for comprehensive outcome assessment.