Management of Pompe disease alongside and beyond ERT: a narrative review

Abstract

Background: Pompe disease is a lysosomal storage disorder that primarily affects muscles, and its natural history has been transformed over the past 20 years by therapies designed to restore the deficient enzyme function, from the first enzyme replacement therapies (ERTs) to the gene therapy currently in development. However, despite these ground-breaking innovations, the importance of a multi-system and rehabilitative approach remains critical, as it addresses the complex systems involved in the disease and optimizes the success of pharmacological treatments.

Methods: We conducted a narrative review of the current pharmacological treatments approved for Pompe disease, as well as those undergoing clinical trials. We also reviewed international recommendations for managing respiratory, musculoskeletal, and cardiac function specially focusing on the late-onset form.

Results: There are no universally agreed guidelines for the multidisciplinary management and many recommendations are based on expert consensus and small interventional studies. Nevertheless, combined approaches involving ERT therapy along with specific rehabilitation and nutritional programs appear to yield beneficial effects.

Conclusions: Pompe disease, one of the first neuromuscular diseases to benefit from the approval of disease-modifying therapies, is a paradigm for the importance of an integrated therapeutic-rehabilitative approach.

Keywords: ERT; LOPD; enzyme-replacement therapy; gene therapy; glycogenosis; late-onset Pompe disease.