A Comprehensive Update on Pompe Disease: From Existing Therapies to Emerging Curative Strategies

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Pompe disease (PD) is an autosomal recessive neuromuscular disorder caused by acid alpha-glucosidase (GAA) deficiency.
• This deficiency leads to glycogen accumulation in muscles, causing infantile-onset (IOPD) and late-onset (LOPD) phenotypes with distinct clinical manifestations.

Purpose of the Study:

• To review recent advances in Pompe disease diagnosis and management.
• To critically evaluate current and next-generation enzyme replacement therapies (ERT).
• To summarize novel therapeutic strategies for Pompe disease.

Main Methods:

• Comprehensive literature review focusing on diagnostic advancements, multisystem involvement, and therapeutic strategies for Pompe disease.
• Critical analysis of current ERT, next-generation ERT (avalglucosidase alfa, cipaglucosidase alfa + miglustat), substrate reduction therapy, and gene therapy.

Main Results:

• Current ERT has improved survival but has limitations including variable efficacy and poor blood-brain barrier penetration.
• Next-generation ERTs show promise in addressing some limitations.
• Emerging therapies like gene therapy offer potential for curative and durable effects, with CNS penetration.

Conclusions:

• Advances in understanding Pompe disease are paving the way for improved diagnostics and treatments.
• Next-generation ERTs and novel strategies like gene therapy hold significant promise for overcoming current therapeutic challenges.
• Future research focuses on curative and CNS-penetrant therapies for Pompe disease.