title: A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years.
abstract: Recombinant human alpha-L-iduronidase (Aldurazyme, laronidase) was approved as an enzyme replacement therapy for patients with the lysosomal storage disorder, mucopolysaccharidosis I (MPS I). In order to assess the long-term safety and efficacy of laronidase therapy, 5 of 10 patients in the original laronidase Phase 1/2 clinical trial were re-evaluated after 6 years of treatment. Lysosomal storage was further improved at 6 years (urinary glycosaminoglycans (GAG) excretion decreased 76%; mean liver size at 1.84% of body weight). Shoulder maximum range of motion was maintained or further increased and reached a mean 33.2 (R) and 25.0 (L) degrees gained in flexion and 34.0 (R) and 27.3 (L) degrees gained in extension. Sleep apnea was decreased in four of five patients and the airway size index improved. Cardiac disease evaluations showed no progression to heart failure or cor pulmonale but pre-existing significant valve disease did progress in some patients. Substantial growth was observed for the pre-pubertal patients, with a gain of 33 cm (27%) in height and a gain of 31 kg in weight (105%). In general, the evaluated patients reported an improved ability to perform normal activities of daily living. Overall these data represent the first evidence that laronidase can stabilize or reverse many aspects of MPS I disease during long-term therapy and that early treatment prior to the development of substantial cardiac and skeletal disease may lead to better outcomes.
authors.affiliation: Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Sifuentes
authors.forename: Robin
authors.initials: R
authors.lastname: Doroshow
authors.forename: Richard
authors.initials: R
authors.lastname: Hoft
authors.forename: Greg
authors.initials: G
authors.lastname: Mason
authors.forename: Irwin
authors.initials: I
authors.lastname: Walot
authors.forename: Michael
authors.initials: M
authors.lastname: Diament
authors.forename: Susan
authors.initials: S
authors.lastname: Okazaki
authors.forename: Kenneth
authors.initials: K
authors.lastname: Huff
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Swiedler
authors.forename: Emil D
authors.initials: ED
authors.lastname: Kakkis
mesh_terms: D000328:Adult; D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000209:etiology; D002648:Child; D005145:Face / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine; D006331:Heart Diseases / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007068:Iduronidase / Q000378:metabolism / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008059:Mucopolysaccharidosis I / Q000150:complications* / Q000188:drug therapy*; D013154:Spleen / Q000473:pathology
chemical_list: D006025:Glycosaminoglycans; D007068:Iduronidase