No abstract

Background Pompe disease is a lysosomal storage disease treated with life-long enzyme replacement therapy (ERT). Home-based ERT has been provided in the Netherlands since 2008 because it diminishes the burden of treatment, increases patient flexibility and autonomy, and is thus a more patient-centred approach to ERT. Methods All Dutch Pompe patients receiving alglucosidase alfa infusions at home were approached to participate in a questionnaire to validate the safety of home-based ERT. Prospective data on symptoms occurring during or within 48 h after infusion and retrospective data on infusion associated reactions (IARs) in the last three months were collected four times during one year. Results In total, 116 out of 120 eligible patients (17 classic infantile, 2 atypical infantile, 15 childhood onset and 82 adult) filled out 423 questionnaires (response rate: 88.1%). Symptoms during or after infusion were reported 27 times in 17 patients. Fatigue was the most commonly reported health complaint (in 9.5% of patients). Four health complaints were judged to be IARs and reported to the Erasmus MC University Medical Center. None of the IARs reported in this study warranted emergency clinical care. Conclusions Our data demonstrate that home-based ERT in Pompe disease can be safely implemented as few, mostly mild, symptoms were reported during or after infusion. Insights from this study can be used as a base for implementing home-based ERT in other countries and to further optimize patient care, as unreported mild symptoms do not pose a health risk but may still be relevant to the patient.

S49 clearance in skeletal and cardiac muscles 12 weeks after treatment. GAA activity in muscle neared wild-type levels at the lowest dose (3 × 10 13 vg/kg). Dose-dependent functional improvements (four-limb hang test) were observed in treated mice by week 12. A GLP toxicology study conducted in non-human primates (NHP) showed that AT845 at the highest doses (> 10 14 vg/kg) caused ALT/AST elevation, a known effect of high-dose AAV systemic administration, but also anti-GAA humoral immune response, elevation in cardiac biomarkers and echocardiogram abnormality. These findings were absent at clinically relevant, lower doses (≤6 × 10 13 vg/kg). Importantly, a full toxicology study carried out with a version of AT845 expressing the Cynomolgus macaque GAA enzyme caused no detectable toxicity and no immune response at comparable doses, indicating that the toxicity observed with AT845 was likely due to an anti-GAA xenogeneic immune response rather than GAA overexpression per se. Overall, our pre-clinical data show that AT845 leads to dose-dependent increases in GAA activity, glycogen clearance and functional improvement in a murine disease model, supporting initiation of clinical trials in Pompe disease.