Pompe disease
(PD) therapeutic options reduce disease burden, however, customized care remains challenging despite these notable treatments, according to a recent review paper.

The review provided an update regarding treatment options for PD to help metabolic and neuromuscular specialists in clinical practice. In doing so, it highlighted recent advancements in enzyme replacement therapy, gene therapy, and substrate reduction therapy.

For all patients with PD, a multidisciplinary shared decision-based method is key in effective management, noted Benedikt Schoser, MD, of the Ludwig Maximilians University, in Munich, Germany, and Pascal Laforet, MD, PhD, of Paris-Saclay University in France.

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“It should also be emphasized that there are no established criteria for poor response to enzyme replacement therapy, significantly beyond 5 years of treatment, when most patients present deterioration of walking abilities and respiratory function,” the authors wrote.

The review paper was recently published in the journal Current Opinion in Neurology.

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This literature review included 31 publications regarding therapeutic strategies and recommendations for adult patients with PD. In total, the researchers identified 3 different treatment options: enzyme replacement therapy, gene therapy, and substrate reduction therapy.

One trial aimed to compare avalglucosidase alfa to alglucosidase alfa, which regardless of showcasing promising results, did perform slightly less optimally overall. Importantly, another study reported improvements in forced vital capacity (FVC), and the 6-minute walk test remained stable in the majority of the individuals.

Synthetic alpha-glucosidase, known as avalglucosidase alfa, generated improvement in FVC at week 49 of follow-up, although 45% of the participants experienced treatment-emergent adverse events, and 16% had serious adverse events. Reactions associated with the infusion of the drug occurred in 26% of the cases.

The benefits of enzyme replacement therapy in these patients are already clear, as stated in published phase 3 trials and other articles that report its long-term effects.

Regarding gene therapy, the first trials aiming to study this option have already begun. Experimental studies successfully induced genes through recombinant adeno-associated virus vectors in mouse models to promote endogenous production of alpha-glucosidase, the enzyme deficient in PD.

The main advantage of gene therapy over enzyme replacement therapy is arguably the biweekly administration scheme and the inability of the synthetic enzyme to cross the blood-brain barrier.

Finally, substrate reduction therapy recently finished preclinical studies to transition into clinical trials. This approach targets glycogen synthase, which appears elevated in mice with PD. Similar techniques have been conducted in other lysosomal storage disorders such as Gaucher and Fabry disease.

Although significant advances for treating individuals with PD have markedly expanded over the past years, there are still multiple gaps of information that need clarification, the authors noted.

“Further evidence on long-term real-world results is needed to implement these new therapies to the expected standard-of-care recommendations,” they concluded.


Schoser B, Laforet P. Therapeutic thoroughfares for adults living with Pompe disease. Curr Opin Neurol. 2022;35(5):645-650. doi:10.1097/wco.0000000000001092