Enzyme Replacement Therapy with Recombinant Human Acid Alpha Glucosidase (Rhgaa) in Infantile Onset Pompe Disease (Iopd)
Resource
NEUROMUSCULAR DISORDERS v.15 n.9-10 pp.712
Journal
NEUROMUSCULAR DISORDERS
Journal Volume
v.15
Journal Issue
n.9-10
Pages
71-2
Date Issued
2005
Date
2005
Author(s)
HWU, WUH-LIANG
Abstract
Introduction: Glycogen Storage disease type 2 (GSD II), also known as Pompe disease is caused by a deficiency of the lysosomal enzyme acid alpha glucosidase (GAA). IOPD is characterized by severe, progressive cardiomyopathy, muscle weakness, respiratory insufficiency, and death usually by 1 year of age. Methods: An open-label, randomized, dose- ranging, multinational, multicenter study of 18 patients with IOPD is being conducted at centers in the US, Europe, Israel and Taiwan. To be enrolled in this trial patients needed to be less than 6 months of age, have cardiomyopathy( defined as an abnormal left ventricular mass index, LVMI) and a residual GAA activity of <1% in skin fibroblasts. Patients were excluded from enrollment if prior to rhGAA they required ventilator support or were in cardiac failure. Patients receive rhGAA derived from CHO cell culture at 20 or 40 mg/kg IV qow. Clinical efficacy end-points include survival, ventilator-free survival, decrease in LVMI, changes in growth (weight and height), and changes in motor development scores. Safety monitoring includes reporting of adverse events, physical examinations, blood and urinary chemistry tests, and anti-rhGAA antibody titers, among others. Results: 11 males and 7 females were enrolled. 7 patients (39%) are Caucasian, 4 (22%) Black, 3 (17%) Asian, 2 (11%) Hispanic, and 2 (11%) Other. The median age at first symptoms was 1.0 months (range: 0–5.5 months) and at first infusion, 5.6 months (range: 1. 2–7.3, uncorrected for prematurity). After 6 months of rhGAA, all 18 patients (100% ) are alive and 17 (94%) are free of invasive-ventilator support. 15 out of 18 patients (83%) developed anti-rhGAA antibodies. Conclusions: Administration of rhGAA for 6 months to this group of patients with IOPD has been generally well tolerated. After 6 months of treatment with rhGAA, patients' age ranges from 7.2 to 13.3 months. Data analyses of all the above-described end points are ongoing. Results of earlier clinical trials evaluating ERT in a small number of patients with IOPD have been promising. This trial will provide information on the safety and efficacy of treatment with CHO cell derived rhGAA to a much larger cohort of patients with IOPD.
SDGs
Type
journal article