“Mainstay treatment” usually refers to a form of therapy that forms an integral part of current treatment strategy; when sufficiently refined, it is usually potent enough to hold back the worst of the symptoms typically expected and generates significant positive clinical impact with minimal harm to the individual. 

In recent years, enzyme replacement therapy (ERT) has emerged as the mainstay treatment for Pompe disease ever since its efficacy has been validated by clinical studies. 

Read more about Pompe disease etiology 

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In 1963, researchers began to develop ERT for the purpose of treating Pompe disease. Early studies were promising, and this led to the large-scale production of recombinant human alpha-glucosidase (rhGAA) in the 1990s. The consensus was that ERT can mostly improve symptoms in individuals with Pompe disease. A subsequent wave of clinical studies aimed to fine-tune the medication and improve its performance. 

In 2006, the Food and Drug Administration (FDA) and the European Medical Agency (EMA) approved ERT (alglucosidase alfa) for the management of patients with Pompe disease. This allowed clinicians to use ERT to treat patients with either infantile-onset Pompe disease (IOPD) or late-onset Pompe disease (LOPD). The real-world use of this medication further elucidated the benefits and limitations of this form of treatment. 

Treatment Outcomes 

In the Journal of Neurology, Sarah and colleagues conducted a clinical study on the effectiveness of ERT in LOPD. 

They sought to compare and quantify the clinical benefit of ERT in patients with LOPD. The main outcomes in their study were motor performance (6MWD) and respiratory function (measured in terms of forced vital capacity). 

Let’s first look at motor  performance. In this study, 407 patients with LOPD were treated with rhGAA. The research team reported that after 18.75 months, individuals on rhGAA had significant improvements in their walking distance compared to baseline. 

In terms of respiratory function, 555 patients were treated with rhGAA. Analysis indicates that after 20.75 months, patients on rhGAA did not demonstrate any significant changes in their breathing capacity, with the forced vital capacity (FVC) remaining stable throughout the observation period. 

Another study looking at muscle strength outcome also reveals no significant changes during the study period. 

“We found that in patients with LOPD, after ERT, the walking distance significantly improved. However, the respiratory function and the muscle strength remained unchanged,” the study authors said.

With such uneven results, it is safe to say that further research is needed in order to understand more deeply how ERT works, as well as the factors that can render it less effective. 

Let’s start with the factors that may impede the ability of ERT in creating the most impact in patients with Pompe disease. One of the clearest ways in which the effects of ERT are blunted is when antibodies are developed against it. This creates a scenario in which the full potency of ERT as a medication is tempered, neutralized. 

Read more about Pompe disease treatment 

Clinicians have identified that the timing by which a patient receives treatment for the first time has consequences on how well patients later respond to treatment. It goes back to an old paradigm in medicine: the commencement of treatment early, even before symptoms appear in earnest, can potentially lead to long-term benefits. Studies indicate that the initiation of treatment soon after identification of disease via newborn screening represents 1 of the best ways to secure excellent outcomes. The goal in early therapy is to obtain better, sustained responses over time. 

There are a small number of patients who may refuse to take ERT at all. However, this is changing; in the 21st century, many individuals from rural areas (globally) are now more open to receiving established Western medicine and seeing them as distinct from any pseudoscientific recommendations that they have otherwise heard of. While old ways of thinking may hold greater sway in certain areas, a growing number of individuals are resisting old, outdated ways of looking at medicine and are embracing a form of medicine borne out of the Western tradition. 

People unshackled by outdated ways of thinking are more likely to check their scientific sources when reading science-heavy articles and are less likely to submit to groupthink. This is a net positive because workers in the frontline understand that many of the so-called “traditional medicine” and “traditional remedies” for Pompe disease simply do not perform better than placebo (with possibly significant adverse effects).

Barring any exceptional medical breakthrough in the coming years, ERT is likely to be routinely prescribed and taken in clinical settings. This is not all bad news: studies indicate that ERT serves as a catalyst in some individuals for taking their first steps to greater personal health. 

Although misinformation is a challenge in every medical setting, the rise of social media has fueled dangerous healthcare trends; so-called “solutions” that are downright quackery are on the rise. As doctors, we must be both realistic and vigilant against the half-truths that are out there that may find their way onto our patients’ phones. 

We can all agree that ERT has brought about a significant leap in the prognosis of all patients willing to undergo this treatment. With grit and hope, we can be confident that future clinical trials will yield even greater forms of treatment, hopefully providing curative solutions for Pompe disease once and for all. 


Sarah B, Giovanna B, Emanuela K, et al. Clinical efficacy of the enzyme replacement therapy in patients with late-onset Pompe disease: a systematic review and a meta-analysisJ Neurol. Published online April 13, 2021. doi:10.1007/s00415-021-10526-5

Pena LDM, Barohn RJ, Byrne BJ, et al. Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: a phase 1, open-label, multicenter, multinational, ascending dose study. Neuromuscul Disord. Published online December 17, 2018. doi:10.1016/j.nmd.2018.12.004