A roadmap for a patient-centred approach to Pompe disease management

TL;DR

This paper outlines a plan for managing Pompe disease through specialized centers that use gene therapy and multidisciplinary care.

Contribution

The paper provides expert-based recommendations for establishing gene therapy centers of excellence for Pompe disease.

Findings

Newborn screening programs should be expanded for infantile-onset Pompe disease.

Specialized multidisciplinary teams are needed to manage patients undergoing gene therapy.

Post-gene therapy monitoring includes adverse event tracking and disease-specific assessments.

Abstract

Pompe disease is a rare, progressive genetic disorder caused by pathogenic variants in the GAA gene. Emerging gene therapies offer the potential for long-term disease management, although logistical and clinical challenges demand specialised centres with defined protocols. A scientific steering committee of 8 European experts deliberated on the requirements for establishing gene therapy centres of excellence for Pompe disease.

A modified think-tank approach was used to develop expert-based recommendations through qualitative research utilizing expert opinion methodology. Discussion topics were validated in an online kick-off meeting. Experts were assigned specific topics and tasked with generating content. Multiple online meetings facilitated expert presentations, discussions, and validation of recommendations for each topic.

Optimised patient management and timely access to treatment require accurate diagnosis and evaluation of Pompe disease. The committee recommended expanding newborn screening programs for infantile-onset Pompe disease and developing protocols for follow-up of presymptomatic late-onset Pompe disease. A specialised multidisciplinary team trained in Pompe disease and gene therapy should manage the patient journey. Pre-gene therapy assessments were recommended to mitigate risks. Patients should be hospitalized and continuously monitored during gene therapy infusions. After gene therapy, guidelines recommend corticosteroid immunosuppression, monitoring for adverse events (including hepatoxicity, myocarditis, thrombocytopenia, thrombotic microangiopathy, and hemophagocytic lymphohistiocytosis), and Pompe disease assessments (including motor functional assessments, magnetic resonance imaging of the muscles, and patient-reported outcomes). Centres of excellence require infrastructure with standard operating procedures for gene therapy products.

Implementing gene therapy for Pompe disease requires a coordinated multidisciplinary effort to overcome gaps in knowledge, infrastructure, and patient management.

The online version contains supplementary material available at 10.1007/s00415-026-13687-3.

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