Effect of enzyme replacement therapy in late onset Pompe disease: open pilot study of 48 weeks follow-up

Abstract

Late-onset Pompe disease (LOPD) is an autosomal recessive disorder caused by deficiency of the enzyme acid glucosidase alfa (GAA). Recently, enzyme replacement therapy (ERT) using recombinant human GAA (rhGAA) became clinically available, and is expected to modify the clinical course in LOPD of various stages. In this study, we evaluated the efficacy and adverse events of ERT for 48 weeks in Korean LOPD patients. Five Korean LOPD patients were included in the study. At baseline, clinical and laboratory features, including muscular and pulmonary function, were assessed, and rhGAA was infused every 2 weeks. Then, patients were examined at every 12-week interval for evaluation of changes in motor and pulmonary function for 48 weeks along with adverse reactions to ERT. The muscular and pulmonary function of the patients varied depending on the baseline condition of the patient after 48 weeks of ERT. However, the overall function of the patients showed stabilization of the disease rather than the improvement seen in infantile-onset Pompe disease. This is the first clinical study on ERT of Korean LOPD patients. Results of our study showed stabilization of muscular and pulmonary function in LOPD patients for 48 weeks with a favorable prognosis for patients who received early diagnosis and ambulatory patients. One of our patients developed a serious anaphylactic reaction, which necessitated the cessation of further ERT. Therefore, our study shows that early diagnosis and ERT are important in preventing further deterioration of the disease.

Muscle imaging data in late-onset Pompe disease reveal a correlation between the pre-existing degree of lipomatous muscle alterations and the efficacy of long-term enzyme replacement therapy

“…Taken together, the results of our study suggest that mildly affected muscles respond better to ERT than severely affected muscles. This is in accordance with findings from clinical studies indicating that the functional outcome is most likely best when ERT is started at an early stage of the disease [16] , [35] . The reasons have not yet been elucidated but a relevant factor may be the increasing impairment of autophagy in skeletal muscle fibers of LOPD patients during disease progression [36] , [37] , as it has been recently shown that the compromised autophagic flux does not only play an essential role in the pathogenesis of Pompe disease but also seems to impair the efficacy of ERT [36] , [37] , [38] .…”

Whole‐body magnetic resonance imaging in late‐onset Pompe disease: Clinical utility and correlation with functional measures

“…With the introduction of new‐born screening, we can expect to see detection of patients with increase in early pre‐clinical stages. If these patients are followed closely and ERT and other interventions are started appropriately, this could result in possibly better outcomes for these individuals …”

“…If these patients are followed closely and ERT and other interventions are started appropriately, this could result in possibly better outcomes for these individuals. 19,20 It is difficult to determine whether ERT plays a role in stabilising the amount of fatty infiltration in muscle. This is often due to a lack of a comparator group.…”

Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients

“…Immune tolerance induction protocols based on high-dose antigen exposure5859 and/or pharmacological interventions60 are valuable tools to manage detrimental humoral immune responses encountered in ERT. Conversely, in LOPD patients, acute reactions to the enzyme are among the most relevant immune complications of ERT6162, thus not warranting the use of immunomodulatory strategies to eradicate anti-GAA antibodies.…”