Safety of Intradiaphragmatic Delivery of Adeno-Associated Virus-Mediated Alpha-Glucosidase (rAAV1-CMV-hGAA) Gene Therapy in Children Affected by Pompe Disease

摘要: A first-in-human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory and neural dysfunction in early-onset Pompe disease was conducted. The primary objective this study assess the safety rAAV1-CMV-hGAA vector delivered diaphragm muscle subjects with ventilatory insufficiency. Safety assessed by measurement change serum chemistries hematology, urinalysis, immune response GAA AAV, as well level health. data demonstrate that AAV treatment safe there were no adverse events related agent. Adverse procedure observed lower baseline neuromuscular function. All resolved before end study, except for one severe event determined not be either agent or procedure. In addition, an anti-capsid anti-transgene antibody all who received rAAV1-CMV-hGAA, concomitant immunomodulation manage reaction enzyme replacement therapy, per their standard care. This observation is significant future studies serves establish a clinically relevant approach blocking responses both capsid protein transgene product.