EMERGING THERAPEUTIC STRATEGIES FOR POMPE DISEASE: A SYSTEMATIC REVIEW OF CURRENT ADVANCES AND FUTURE DIRECTIONS

Lindsay Joanne M. Yuzon; Rizza B. Aguilar; Christabelle A. Miranda; Gecelene C. Estorico

doi:10.5281/zenodo.21319117

Abstract

Emerging therapeutic strategies for Pompe disease have gained increasing attention as researchers seek to overcome the limitations of conventional enzyme replacement therapy (ERT), which include inadequate skeletal muscle uptake, immune responses, and lifelong dependence on intravenous infusions. Following the PRISMA 2020 guidelines, literature was retrieved from PubMed, ScienceDirect, Wiley Online Library, Taylor & Francis, MDPI, Frontiers, Cell Press, Bentham Science, and other peer-reviewed databases. Sixteen eligible studies consisting of systematic reviews, narrative reviews, clinical trials, and original research articles were analyzed to evaluate current and developing treatment approaches for Pompe disease. The reviewed evidence highlights significant advances in next-generation enzyme replacement therapies, adeno-associated virus (AAV)-mediated gene therapy, pharmacological chaperones, substrate reduction therapy, antisense oligonucleotide therapy, and prenatal therapeutic interventions. Gene therapy emerged as one of the most promising strategies because of its potential to provide sustained acid alpha-glucosidase (GAA) expression after a single administration, while combination therapies demonstrated improved enzyme stability and skeletal muscle targeting compared with conventional ERT. Although several emerging therapies have shown encouraging clinical and preclinical outcomes, long-term safety, efficacy, accessibility, and cost-effectiveness remain important challenges. Overall, these advances represent significant progress toward more effective and durable treatment options for Pompe disease while emphasizing the need for continued clinical research to optimize patient outcomes.

Keywords

Pompe disease; acid alpha-glucosidase (GAA); enzyme replacement therapy; gene therapy; pharmacological chaperones; substrate reduction therapy; systematic review.

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