Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease:: results of a phase II clinical trial

Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy. We report on the results of a phase II clinical trial including two patients with classical infantile Pompe disease receiving enzyme replacement therapy over a period of 48 weeks by weekly infusions. Recombinant acid alpha-glucosidase was derived from the milk of transgenic rabbits. Safety was evaluated by recording adverse events while clinical efficacy was evaluated by ventilator-free survival. left ventricular mass index, motor development as well as histologic and biochemical analysis of muscle biopsies. This therapy was in general well-tolerated. There was an overall improvement in left ventricular mass, cardiac function, skeletal muscle function and histological appearance of skeletal muscle. (C) 2004 Elsevier B.V. All rights reserved.