New therapeutic approaches for Pompe disease: enzyme replacement therapy and beyond

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Pompe disease is a rare, inherited metabolic disorder caused by acid alpha-glucosidase (GAA) deficiency.
• It leads to glycogen accumulation, primarily affecting cardiac and skeletal muscles.
• Historically, Pompe disease management was palliative, with severe infantile cases rarely surviving past one year.

Purpose of the Study:

• To review the impact and lessons learned from enzyme replacement therapy (ERT) in Pompe disease.
• To discuss the limitations of current ERT and explore novel therapeutic strategies.
• To highlight factors influencing treatment outcomes in both infantile and late-onset Pompe disease.

Main Methods:

• Review of clinical data and published literature on alglucosidase alfa (ERT) for Pompe disease.
• Analysis of outcomes in infants and adults with Pompe disease receiving ERT.
• Exploration of emerging therapeutic approaches, including gene therapy and substrate reduction.

Main Results:

• ERT with alglucosidase alfa has significantly improved survival, cardiac function, and motor development in infants with Pompe disease.
• ERT has stabilized disease progression and improved motor and pulmonary function in late-onset Pompe disease.
• Treatment outcomes are influenced by age at ERT initiation, genotype, and multidisciplinary care.

Conclusions:

• Enzyme replacement therapy represents a significant advancement in Pompe disease management.
• Further research is needed to overcome ERT limitations and develop more effective treatments.
• Adjunctive and alternative therapies, including gene therapy, hold promise for future Pompe disease treatment.