James Edward Wraith

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Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Clinical manifestations include severe airway obstruction, skeletal deformities,(More)
BACKGROUND Niemann-Pick type C disease (NPC) is an inherited neurodegenerative disorder characterised by an intracellular lipid-trafficking defect with secondary accumulation of glycosphingolipids. Miglustat, a small iminosugar, reversibly inhibits glucosylceramide synthase, which catalyses the first committed step of glycosphingolipid synthesis. Miglustat(More)
OBJECTIVE To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I). STUDY DESIGN This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary(More)
OBJECTIVE Our goal was to evaluate the long-term safety and efficacy of recombinant human alpha-l-iduronidase (laronidase) in patients with mucopolysaccharidosis I. PATIENTS AND METHODS All 45 patients who completed a 26-week, double-blind, placebo-controlled trial of laronidase were enrolled in a 3.5-year open-label extension study. Mean patient age at(More)
OBJECTIVE Disease management for mucopolysaccharidosis type I has been inconsistent because of disease rarity (approximately 1 case per 100,000 live births), phenotypic heterogeneity, and limited therapeutic options. The availability of hematopoietic stem cell transplantation and the recent introduction of enzyme replacement therapy for(More)
BACKGROUND Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid alpha-glucosidase (GAA). Infantile-onset Pompe disease is characterized by cardiomyopathy, respiratory and skeletal muscle weakness, and early death. The safety and efficacy of recombinant human (rh) GAA were evaluated in 18 patients with(More)
Purpose: To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II.Methods: Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase(More)
Niemann-Pick disease type C (NP-C) is a lysosomal storage disease in which impaired intracellular lipid trafficking leads to excess storage of cholesterol and glycosphingolipids in the brain and other tissues. It is characterized clinically by a variety of progressive, disabling neurological symptoms including clumsiness, limb and gait ataxia, dysarthria,(More)
Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a lysosomal storage disease that is characterized by systemic clinical manifestations and significant functional impairment. Diagnosis and management are often challenging because of the considerable variability in symptom presentation and rate of progression. The optimal standard of care should be based(More)
Niemann–Pick disease type C (NPC) is an autosomal recessive, neurovisceral lipid storage disorder. Mutations in two genes (NPC1 and NPC2) produce indistinguishable clinical phenotypes by biochemical mechanisms that have not yet been entirely clarified. The wide spectrum of clinical presentations of NPC includes hepatic and pulmonary disease as well as a(More)